Catherine - LifeDNA

Genetics of Salla Disease: Mutations, Inheritance and Gene Therapy

Catherine on March 15, 2025

Disclaimer: This article is for informational purposes only and is not intended for diagnostic use. LifeDNA does not provide diagnostic reports on any traits discussed. Genetics is just one piece of the puzzle; please consult a healthcare professional for comprehensive guidance on any health condition.

Salla disease is a rare autosomal recessive lysosomal storage disorder characterized by defective sialic acid metabolism. It falls under the broader category of sialic acid storage disorders (SASD) and is caused by mutations in the SLC17A5 gene, which encodes the sialin transporter protein. This transporter is responsible for the export of free sialic acid (N-acetylneuraminic acid) from lysosomes. Mutations in SLC17A5 lead to an abnormal accumulation of sialic acid within lysosomes, affecting multiple organ systems, particularly the central nervous system.

Sialic acids are important for cell signaling, immune function, and neural development, and their proper export allows cells to recycle them for glycoprotein and glycolipid synthesis. Defective transport impairs cellular function, particularly in the nervous system, leading to severe neurodevelopmental and metabolic disorders.

Genetic Basis of Salla Disease

SLC17A5 Gene and Its Role

The SLC17A5 (a.k.a AST) gene, located on chromosome 6q14-q15, encodes sialin, a protein essential for transporting sialic acid out of lysosomes.

In Salla disease, mutations in SLC17A5 impair this transport, leading to accumulation of sialic acid inside cells and subsequent cellular dysfunction. The disease follows an autosomal recessive inheritance pattern, meaning an affected individual must inherit two defective copies of the SLC17A5 gene—one from each parent.

Common Mutations in SLC17A5

Several mutations in SLC17A5 have been linked to Salla disease, with the most common being:

c.115C>T (p.R39C): A prevalent mutation in Finnish populations, often associated with classical Salla disease.
c.850C>T (p.Q284X): A nonsense mutation leading to a truncated, non-functional sialin protein.
c.1408G>A (p.G470R): A missense mutation affecting protein stability.

Clinical Manifestations

The severity of Salla disease varies based on the residual function of the mutated sialin transporter. There are two primary forms:

Classical Salla Disease (CSD) – Milder form, primarily observed in Finnish populations, presenting with early-onset hypotonia, delayed motor development, progressive neurological deterioration, and intellectual disability.
Infantile Sialic Acid Storage Disorder (ISSD) – A more severe neonatal-onset form, often leading to fatal multi-organ involvement and profound neurodevelopmental impairment within infancy.

Diagnosis and Genetic Testing

Diagnosis of Salla disease is confirmed through:

Urinary Free Sialic Acid Testing – Elevated free sialic acid in urine is a hallmark of the disease.
Molecular Genetic Testing – Identification of SLC17A5 mutations through next-generation sequencing (NGS) or Sanger sequencing.
Brain MRI – May reveal characteristic white matter abnormalities, indicative of leukoencephalopathy.

Genetic Counseling and Inheritance

As an autosomal recessive disorder, parents of an affected child are typically carriers (heterozygous), each having one defective copy of SLC17A5. Carrier parents have a 25% chance of passing the disease to their offspring with each pregnancy, a 50% chance that the child will be an asymptomatic carrier, and a 25% chance of being unaffected.

Also learn about other autosomal recessive disorders:

Cystic Fibrosis

Genetic counseling is highly recommended for families with a history of Salla disease, especially in high-risk populations such as those of Finnish descent.

Potential Therapeutic Approaches

A 2023 study compared two methods, the CRISPR-Cas9-mediated homology-directed repair (HDR) and adenine base editing (ABE), to correct the SLC17A5 c.115C>T (p.Arg39Cys) variant in human fibroblasts. While HDR showed minimal correction with a high rate of undesired mutations, ABE achieved significant correction without detectable errors, effectively reducing free sialic acid levels and offering a glimpse of hope that one day this methodology could be applied to help affected individuals as well.

Learn more about the groundbreaking usage of Gene Editing to cure genetic conditions

Currently, there is no cure for Salla disease, and treatment focuses on symptom management and supportive care, including:

Physical therapy for motor function support.
Speech and occupational therapy for developmental delays.
Seizure management with antiepileptic medications.
Future gene therapy prospects – Research into gene therapy and targeted molecular treatments may provide potential interventions in the future.

Conclusion

Salla disease is a rare lysosomal storage disorder caused by mutations in the SLC17A5 gene, leading to defective sialic acid transport and progressive neurological impairment. While currently incurable, early diagnosis, genetic counseling, and supportive therapies can improve quality of life for affected individuals. Advances in molecular genetics continue to offer hope for future treatments, highlighting the importance of ongoing research in the field of lysosomal storage diseases.

References

What You Should Know About Bulimia and Its Health Effects

Catherine on March 13, 2025

Bulimia nervosa, often just called bulimia, is a serious eating disorder that can affect both mental and physical health. While it can impact anyone, it is most commonly seen in females and usually begins in adolescence or early adulthood. Between 1% and 2% of people may experience bulimia in any given year. The condition can be life-threatening if left untreated, so it is important to understand what it is, what causes it, and how it can be managed.

What Is Bulimia Nervosa?

Bulimia nervosa is a mental health condition that involves a cycle of binge eating followed by unhealthy actions to avoid weight gain. People with bulimia often eat large amounts of food in a short time, feeling unable to stop themselves. This bingeing is usually followed by purging, which may include vomiting, fasting, or excessive exercise. These behaviors are often done in secret, leading to feelings of shame, guilt, and emotional distress.

The condition was first described in a scientific paper in 1979 by psychiatrist Gerald Russell, who considered it to be a more dangerous form of anorexia. Over time, bulimia has been recognized as its own distinct disorder with specific signs and treatment approaches

You may also want to read: Genetic Influences of Unhealthy Food Intake

Who Does Bulimia Affect?

Bulimia may affect individuals of any age, gender, or background, but it is most commonly seen in adolescent girls and young women. The disorder typically begins during the teenage years or early adulthood, though it may also develop later in life. While the majority of cases are reported among females, bulimia may also affect males.

What Are the Symptoms of Bulimia?

Recognizing the symptoms of bulimia can be challenging, as individuals with this disorder often go to great lengths to hide their behaviors. However, there are both emotional and physical signs that may indicate the presence of bulimia.

Behavioral and Emotional Symptoms

Fear of gaining weight and frequent dieting: Individuals with bulimia are often afraid of a change of weight and engage in constant dieting or extreme weight control measures.
Eating unusually large amounts of food in one sitting: Binge eating is a key symptom of bulimia, where individuals consume an excessive amount of food in a short period.
Feeling a loss of control while eating: During a binge, individuals may feel they cannot stop eating even if they want to.
Being unhappy with body weight or shape: Bulimia often comes with a distorted body image, where the individual feels dissatisfied with their appearance.
Extreme mood swings or low self-esteem: Bulimia is frequently linked to intense mood swings, anxiety, and low self-worth, which contribute to the behaviors associated with the disorder.

Physical Symptoms

Dental problems: Frequent vomiting exposes the teeth to stomach acid, leading to enamel erosion, cavities, and gum disease.
Digestive issues: Bulimia can cause constipation, acid reflux, and other digestive problems due to laxative abuse and frequent purging.
Scars or calluses on the knuckles: People who induce vomiting may develop noticeable scars or calluses on the back of their hands from repeatedly forcing their fingers down their throat.
Dehydration and muscle weakness: Purging and laxative use can lead to dehydration, resulting in fatigue, muscle weakness, and even heart problems in severe cases.

What Are the Health Effects of Bulimia?

Bulimia can cause serious health problems that affect both the body and the mind. These complications are the result of the repeated cycle of bingeing and purging, which puts stress on the body’s systems. If not treated, these issues can become life-threatening.

Mental health issues: People with bulimia are at higher risk for depression, anxiety, and personality disorders.
Substance misuse and self-harming behaviors: Some may turn to drugs or alcohol to cope with emotional pain, or engage in self-harming behaviors like cutting or burning themselves.
Suicidal thoughts or actions: In extreme cases, the overwhelming stress and emotional distress can lead to suicidal thoughts or attempts.

What Are the Causes of Bulimia?

The exact cause of bulimia isn’t fully known, but experts believe it is linked to a mix of genetic, emotional, and environmental factors. People who have close family members with eating disorders may be more likely to develop bulimia.

Emotional health plays a major role. Conditions like depression, anxiety, and low self-esteem are commonly seen in people with bulimia. Traumatic events or childhood mistreatment can also increase the risk. In many cases, people turn to food as a way to cope with stress or emotional pain. The media and popular culture often promote unrealistic body types, especially for women. Constant exposure to these messages can lead to body dissatisfaction and a desire to control weight in unhealthy ways. Peer pressure, bullying, or teasing about body image can also trigger the disorder, especially during teenage years. Dieting itself is a known risk factor. People who frequently restrict calories may end up binge eating due to hunger, then feel guilty and try to compensate by purging. This cycle may quickly spiral into a long-term eating disorder.

Genetics on Bulimia

Research into the genetics of eating disorders, including bulimia has shown that these conditions may have a strong genetic component, rather than being solely influenced by social or cultural factors. Studies suggest that bulimia and other eating disorders, like anorexia nervosa, are influenced by a combination of genetic and environmental factors

Studies on families and twins have shown that eating disorders like bulimia often run in families. This means that if someone has a relative with an eating disorder, they are more likely to develop one too. Twin studies have found that heritability may explain between 54% to 83% of the risk for developing bulimia. This suggests that genetics play a big role in who gets the disorder.

Research studies also show that some people may be born with a higher chance of developing behaviors linked to bulimia, like binge eating and purging. Genetics may also influence personality traits often seen in people with bulimia, such as perfectionism, anxiety, and being highly sensitive to stress. These traits are also common in other mental health issues, like depression and anxiety, which may share some of the same genetic roots with bulimia.

Studies support the idea that bulimia is not only caused by outside pressures like media or dieting. Instead, it has strong genetic factors that shape both a person’s mental health and behavior. More research is still needed to find the exact genes involved, which could help lead to better ways to treat and understand the disorder.

Is Bulimia Hereditary?

Yes, bulimia is strongly influenced by genetics. Studies show that it often runs in families. If someone has a close relative with bulimia, their risk of developing it increases by 7 to 12 times. Twin studies also confirm this—identical twins are more likely to both have bulimia compared to fraternal twins. Overall, researchers estimate that 54% to 83% of the risk for bulimia comes from inherited genetic factors.

How Is Bulimia Diagnosed?

To diagnose bulimia, a professional healthcare provider will ask about eating habits, emotions, and physical symptoms. They will also perform a physical exam. There are no lab tests that specifically confirm bulimia, but tests like blood work, urinalysis, and heart monitoring may be done to check for damage caused by the disorder.

Diagnosis typically follows specific criteria. These include having repeated episodes of binge eating, feeling out of control during those episodes, using purging behaviors, and experiencing these behaviors at least once a week for three months. Another important sign is allowing body shape or weight to strongly affect self-image.

Being honest during the evaluation process is important. Although it may feel uncomfortable, sharing the full picture helps doctors recommend the right treatment.

How Is Bulimia Treated?

Effective treatment for bulimia usually involves a combination of therapies and support. The goal is to stop the binge-purge cycle and address the thoughts and emotions that lead to it.

Psychotherapy, especially cognitive-behavioral therapy (CBT), is one of the most common treatments. CBT helps people recognize harmful thinking patterns and replace them with healthier behaviors. It also teaches skills to cope with difficult situations without turning to food.

Nutritional counseling is also key. A dietitian or counselor can help build balanced eating habits and develop a healthy relationship with food. This helps prevent bingeing by reducing food restriction. In some cases, medications such as antidepressants may be prescribed. These can help reduce binge eating and treat underlying issues like anxiety or depression. Support groups can also provide encouragement and understanding. Sharing experiences with others who are going through similar challenges can be a powerful part of recovery.

References

Is Emotional Quotient (Intelligence) in Your DNA? The Genetic Side of EQ

Catherine on March 8, 2025

You’ve probably heard that being “book smart” isn’t enough to do well in life. But what if your ability to understand emotions and bounce back from stress is something you’re actually born with? Emotional Intelligence Statistics reveal that Emotional Quotient or EQ drives over 60% of personal and professional success, and may even account for 70% of a person’s life achievements. On top of that, people with high EQ enjoy better mental health and less daily stress. So, could emotional intelligence be hardwired into your genes? In this article, we uncover the genetic side of EQ and how it may shape your emotional health.

What Is Emotional Quotient?

Emotional intelligence, often called EQ, is the ability to recognize, understand, and manage your emotions, as well as the emotions of others. It’s not just about being aware of how you feel. It’s about knowing why you feel that way and how those emotions influence your behavior.

You may also want to read: Is Intelligence Genetic?

What Makes Up Emotional Quotient?

There are five key components of emotional intelligence, and these skills are important in every part of life, from your career to your personal relationships. When you develop emotional intelligence, it helps you communicate better, resolve conflicts more effectively, and support your overall emotional well-being. Here are the five components:

Self-Awareness: When you are self-aware, you can identify what you’re feeling in the moment and why you’re feeling that way. This helps you see how your emotions influence your actions, decisions, and interactions with others. Self-awareness allows you to recognize both your strengths and weaknesses, giving you the insight to grow, make better choices, and respond thoughtfully instead of reacting impulsively.

Self-Regulation: This is the ability to manage and control your emotional responses, especially in challenging or stressful situations. It doesn’t mean suppressing emotions but learning how to express them appropriately and constructively. People who practice self-regulation can pause and think before reacting, stay calm under pressure, and avoid making impulsive decisions they might regret. This skill helps create emotional balance, allowing you to stay focused, adaptable, and in control of your behavior, even when emotions are running high.

Motivation: refers to the inner drive that pushes you to pursue goals and improve yourself—not because of external rewards, but because you find purpose and satisfaction in what you’re doing. People with high emotional intelligence are usually self-motivated; they set personal goals, stay positive, and bounce back from setbacks. This kind of motivation is fueled by passion, curiosity, and a desire for growth, helping individuals stay focused and determined even when facing obstacles.

Empathy: goes beyond sympathy or simply feeling sorry for someone—it’s about putting yourself in another person’s shoes and seeing things from their perspective. When you practice empathy, you become more sensitive to how others are feeling, which helps you respond with care, kindness, and respect. Empathy is crucial in building meaningful relationships, resolving conflicts, and creating a supportive environment, whether at work, at home, or in your community.

Social Skills: are the abilities that help you communicate, connect, and interact effectively with others. They include listening actively, expressing yourself clearly, managing conflict, and working well in a team. Good social skills allow you to build strong, healthy relationships and navigate social situations with ease. People with high emotional intelligence use their social skills to influence, inspire, and support others while fostering collaboration and trust in both personal and professional settings.

Genetics on Emotional Quotient

Researchers in Russia recently explored whether certain genes could affect a person’s emotional intelligence or emotional quotient. The study focused on four genes: COMT, BDNF, DRD2, and HTR2A. To measure emotional intelligence accurately, they used the Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT). This method is considered more reliable than self-reported questionnaires because it evaluates real emotional skills rather than personal opinions.

Their results showed some interesting connections. The COMT gene, which influences how long brain chemicals like dopamine stay active, appeared to play a role. People who had the heterozygous Val158Met genotype (SNP rs4680-AG) in this gene scored higher on emotional intelligence tests. This specific genetic variant may help people regulate their emotions better and stay focused when recognizing emotions in others.

When looking at the BDNF gene, which is involved in brain flexibility and learning, the researchers found no clear link to emotional intelligence, although earlier studies suggested there might be a connection.

Another dopamin-related gene they examined was DRD2, which affects the number of dopamine D2 receptors in the brain. These receptors are important for motivation, reward, and emotional processing. The study found that people with the CC genotype of the SNP rs1800497 near the DRD2 gene, who have more dopamine receptors, scored higher on emotional intelligence tests. On the other hand, those with the CT genotype had lower scores. Previous research has also shown that having fewer dopamine receptors may be linked to emotional difficulties and a higher risk of developing addictions.

The final gene studied was HTR2A, which is related to serotonin receptors. Serotonin is another brain chemical that helps regulate mood and emotions. The researchers discovered that people with the AA genotype of the SNP rs6311 near this gene scored higher on emotional intelligence tests, while those with the GG genotype scored lower. It is possible that the homozygous AA variant helps the brain have more serotonin receptors, making it easier to understand and manage emotions.

The study showed that some people may naturally find it easier to handle emotions because of their genetics, especially due to variants in genes related to dopamine and serotonin—chemicals often called the brain’s “feel-good” messengers. However, the researchers also pointed out that emotional intelligence is not only shaped by genetics. Life experiences, education, and training play a big role in developing these skills.

Knowing how genetic variation might influence emotional intelligence can help explain why some people are naturally better at handling emotions, but it also shows that anyone can improve with the right support and practice.

Is Emotional Intelligence Something You Inherit?

While there may be some genetic influence on emotional intelligence, it is not the whole story. Unlike IQ, which stays mostly the same throughout adulthood and is largely inherited, emotional quotient is made up of many skills that can be learned and improved over time.

In fact, developing emotional intelligence is similar to learning any other skill. With practice and willingness to change, anyone can become better at recognizing emotions, managing feelings, and building stronger relationships. Studies have even shown that training can improve a person’s emotional intelligence and that these improvements can last for months. So, emotional intelligence is not totally fixed at birth. You can definitely strengthen your EQ through learning, practice, and being open to personal growth.

Can You Boost Your Emotional Quotient?

While some parts of emotional intelligence may be shaped by your genes, much of it can be learned and improved through practice. If you want to strengthen your emotional intelligence, here are some useful steps:

Start by understanding your emotions: Pay attention to how you feel in different situations. Try to identify your emotions and understand why you feel that way. Being able to recognize your feelings is the first step toward managing them better.
Ask people around you how they see you: Sometimes, we don’t realize how we react to stress, criticism, or emotional situations. Getting feedback from people you trust—whether it’s friends, family, or coworkers—can help you see things from another perspective. This can show you where you’re doing well and where you might need to grow.
Read and learn from different perspectives: Reading stories, books, or articles about people’s lives and experiences can help you understand how others think and feel. When you learn about the challenges and emotions of others, it becomes easier to develop empathy and connect with people in real life.
Encourage emotional awareness in others: If you want to create a space where emotional intelligence is valued—whether at home, school, or work—lead by example. Be open, respectful, and kind in how you communicate. Recognize and appreciate people who show empathy, teamwork, or emotional maturity. When positive behavior is noticed and encouraged, it inspires others to improve too.

References

Genetics of Left-Handedness and Health Connection

Catherine on March 4, 2025

Only up to 10% of people are left-handed, so the rest, about 90% are right-handed. And a rare 1% are ambidextrous, meaning they can use both hands equally well. But is being left-handed just a random trait, or is there more to it? Turns out, genetics may play a part. Studies suggest left-handed people may also have unique brain wiring, differences in immune function, and even some varying health risks compared to right-handers.

Understanding these connections may help us learn more about how the brain and body work together, giving left-handed individuals important insights into one’s health.

You may want to read: Genetics and Grip: Understanding the Role of DNA in Hand Strength

What Is Handedness?

Handedness refers to the preference most people show for using one hand over the other for tasks like writing, eating, or throwing. The majority of the population is right-handed, meaning they favor their right hand for these tasks. On the other hand, left-handedness, a preference for the left hand, is seen in about 10% of the population.

The study of handedness involves understanding the relationship between brain structure and function, particularly how the two hemispheres of the brain control different motor functions. The left hemisphere generally controls the right side of the body, and vice versa. However, handedness isn’t just a matter of left or right, it’s influenced by a mix of genetics, brain function, and environmental factors.

What Is Left-Handedness?

Left-handedness is a trait in which an individual prefers using their left hand for most tasks, including writing, throwing, and other fine motor skills. Unlike the majority of people who are right-handed, left-handed individuals often have the opposite dominant hand. While handedness might appear to be a simple preference, it might be linked to deeper biological processes, particularly in the brain.

The left hemisphere of the brain typically controls the right side of the body, and the right hemisphere controls the left side. In most right-handed individuals, language and fine motor skills are controlled by the left hemisphere, whereas for left-handed people, these functions can be more evenly distributed or even shifted to the right hemisphere. This unique characteristic in left-handed people often leads to different patterns of brain development and organization.

What Causes Left-Handedness?

The exact cause of left-handedness is still unclear, but scientists believe it’s shaped by a mix of genetics, brain structure, and environment. Instead of a single “left-handed gene,” research suggests that multiple genes play a role, especially those involved in brain development.

What Are the Traits of Left-Handedness?

Left-handedness isn’t a medical condition, but it is linked to certain physical and cognitive traits:

Physical Traits

Distinctive Motor Skills: Left-handed individuals may have different hand movements for activities like writing, eating, or playing sports.
Hand-Eye Coordination Differences: Since most tools and instruments are designed for right-handed users, left-handed people may need to adapt their coordination.
Adjustment to Right-Handed Environments: Everyday tasks, such as using scissors, computer mice, or musical instruments, can be more challenging due to right-hand-dominant designs.

Cognitive Traits

Brain Function and Lateralization Differences: Left-handed people often show a greater ability to use both hemispheres of the brain for tasks like language processing and problem-solving.
Stronger Spatial Reasoning: Some studies suggest that left-handers may excel in areas requiring spatial awareness, such as art, architecture, and mathematics.
Enhanced Creativity and Divergent Thinking: Left-handers are often linked to creative problem-solving and unique thinking patterns.

Is Left-Handedness Inheritable?

Left-handedness can be inherited, but it’s not determined by just one gene. Instead, it is influenced by a combination of several genes and environmental factors. Research shows that left-handedness tends to run in families, meaning that if one parent is left-handed, their child is more likely to be left-handed too, though it’s not guaranteed. Identical twins are more likely to both be left-handed compared to fraternal twins, which also suggests there’s a genetic component at play.

However, genetics isn’t the only factor. A study involving over 25,000 twin pairs found that the preferred hand for writing or drawing is a weak genetic trait, with a heritability of just 24%. This indicates that while there’s a genetic influence, other factors also play a significant role in determining handedness.

What Are the Genetic Connections of Left-Handedness?

Several genes have been implicated in the development of handedness. LRRTM1, a gene involved in brain development, has been shown to be associated with left-handedness. Studies have suggested that mutations or variants in this gene can affect how the brain’s hemispheres are organized, potentially leading to a preference for the left hand.

Another gene, DYX1C1 (or DNAAF4), which is associated with dyslexia and other learning disabilities, has also been linked to handedness. This gene plays a role in the migration of neurons in the brain, and disruptions in its function can affect brain asymmetry and the development of lateralization. Similarly, KIAA0319, a gene implicated in dyslexia, has been found to be associated with handedness. Disruptions in these genes may impact brain organization and contribute to the development of left-handedness.

It is important to note that the genetic influence on handedness is likely polygenic, meaning that multiple genes contribute to the trait, and these genes interact with environmental factors in complex ways. Therefore, while certain genetic markers may increase the likelihood of a person being left-handed, no single gene is solely responsible.

What Are the Health Issues Associated with Left-Handedness?

While there are some health risks associated with left-handedness, such as an increased likelihood of certain conditions like schizophrenia, heart disease, and breast cancer, many of these findings are still debated.

Neurological Disorders: Left-handed individuals have a slightly higher incidence of certain neurological disorders such as schizophrenia and epilepsy. This may be due to differences in brain asymmetry and how the two hemispheres communicate. The right hemisphere dominance seen in some left-handed individuals could contribute to these conditions.
Learning Disabilities: Left-handed individuals have a higher likelihood of developing dyslexia and other learning disabilities. These conditions are thought to be linked to differences in how the brain processes language and motor functions. Some dyslexia-related genes, such as DYX1C1, have been found to overlap with those associated with left-handedness.
Motor Coordination Issues: Left-handed individuals may experience challenges with motor coordination due to the predominance of right-handed tools and environments. However, these issues are generally mild and do not significantly impair daily functioning.
Left-Handedness and Breast Cancer: Older studies have suggested that left-handed individuals might have a higher risk of breast cancer, with some indicating that it develops earlier in left-handed people. However, more recent research has been inconclusive, and the link between estrogen exposure in the womb and left-handedness has not been proven.
Left-Handedness and Schizophrenia: A number of studies have found that left-handed individuals may be more likely to develop schizophrenia. This connection may be due to differences in brain organization, with left-handed people exhibiting less lateralization (specialization) between the brain’s hemispheres, a feature often associated with schizophrenia. Further research has supported this, showing a higher incidence of mixed-handedness in those with schizophrenia.
Left-Handedness and Mental Health: Research has shown that left-handed people may experience certain mental health symptoms, including mood swings, anxiety, and irritability. Mixed-handedness has been more strongly linked to conditions like PTSD, though the evidence for depression in left-handed individuals is minimal.
Left-Handedness and Alcohol Consumption: Though some earlier research proposed that left-handed individuals drink more alcohol, a 2022 study found no significant correlation. Previous findings may have been influenced by societal biases and stigma.
Left-Handedness and Heart Disease:Recent studies have raised concerns that left-handed individuals may have a higher risk of cardiovascular disease. However, no clear cause has been identified, and more research is needed to determine why this might be the case.

The LifeDNA Reports and Your Genetic Health

The LifeDNAReports provide personalized insights into how your genetic makeup influences various aspects of your well-being, including nutrition, fitness, sleep, and personality and cognition. By understanding these genetic influences, you can make more informed choices about your lifestyle and wellness.

Whether you’re left-handed or just curious about how your genes shape your handedness, the LifeDNA Wellness Report provides important information on many interesting genetic traits. Our Report looks at your genetic make-up to help you understand your strengths, potential risks, and how you can improve your wellness. This way, you can make better choices based on your unique genetic makeup. Get yours here.

References

Is Sensitivity to Stress Genetic?

Catherine on March 2, 2025

Some people seem to handle life’s ups and downs without much trouble, while others feel overwhelmed by even small challenges. This difference in how people react to stress is called stress sensitivity. It’s the reason why certain individuals experience stronger emotional or physical reactions when facing pressure, change, or adversity. Stress sensitivity isn’t random, it’s shaped by a combination of genetics, life experiences, and daily habits.

Understanding what makes someone more sensitive to stress is important because it may affect both mental and physical health. By recognizing the factors behind the sensitivity of stress, people can take steps to better manage their stress, improve their well-being, and prevent long-term health issues.

What Is Sensitivity to Stress?

Sensitivity to stress refers to how strongly a person’s body and mind respond to stressors. While everyone experiences stress, people with high stress sensitivity may have heightened emotional reactions, feel physically drained, or struggle to bounce back after stressful events. Their nervous system may be more reactive, making everyday stressors feel intense and exhausting. This is different from typical experience of stress, which is usually manageable and temporary.

You may also want to read: Can Quercetin Enhance Stress Response in People?

Is Sensitivity to Stress Caused by Environmental Factors?

A person’s environment and life experiences may also increase stress sensitivity. Early childhood experiences, such as trauma, neglect, or living in a high-stress household, can shape how the brain and body respond to stress later in life. Chronic exposure to stressful situations whether at work, school, or in relationships may keep the body’s stress response system in overdrive. Over time, this constant activation can make it harder to cope with new stressors.

Lifestyle choices like diet, sleep, exercise, and social support also influence how sensitive someone is to stress. For example, poor sleep, lack of physical activity, or unhealthy eating habits can reduce stress resilience. Additionally, epigenetic changes, which are chemical modifications that affect how genes work without altering the DNA sequence itself may increase stress sensitivity. These changes may occur due to long-term stress, trauma, or even diet and may be passed down to future generations.

Is Sensitivity to Stress Caused by Genetics?

Our ability to handle stress isn’t just shaped by our environment, it’s also influenced by our genes. Some people are naturally more sensitive to stress because of certain genetic variations that affect how the brain and body respond to challenging situations. These genes may influence how the stress hormone cortisol is regulated, how emotions are processed, and even how resilient a person feels in stressful times.

Two important genes linked to stress are FKBP5 and COMT according to a 2020 study. These genes affect how the brain and body manage stress, emotions, and recovery after stressful events.

The FKBP5 gene may play a role in regulating the body’s stress hormone, cortisol. Certain versions of FKBP5 can cause the body to struggle with calming down after a stressful situation, leading to a stronger or longer-lasting stress response. Similarly, the COMT gene, which is involved in breaking down the brain chemical dopamine, can also influence stress sensitivity. A common variation in COMT, known as Val158Met, affects how efficiently dopamine is cleared from the brain. People with this variation may feel more emotionally reactive or struggle with stress regulation, especially if they experienced childhood stress or trauma.

These genetic differences don’t guarantee someone will have stress-related health issues. Instead, they interact with life experiences. For example, a person with these gene variants who faced early life adversity may be more likely to develop anxiety, depression, or impulsive behaviors. On the other hand, a supportive environment can help reduce the impact of these genetic risks.

A very recent study shows that a specific gene change in the CD38 gene may affect how people react emotionally to stressful situations. This research, published in Scientific Reports, looked at a small change (SNP) in the CD38 gene called rs3796863. This change can influence how sensitive a person is to emotional stress.

The CD38 gene helps control the release of oxytocin, which is a hormone involved in social bonding, empathy, and emotional balance. People who have the A-allele in the SNP rs3796863 often have higher oxytocin levels. They may feel more empathy and care deeply about others. However, studies also found that people with the A-allele tend to feel more emotional distress, sadness, or even feel socially isolated when facing stressful situations.

To better understand this, researchers studied 171 university students in Canada. They showed them an emotional video of a father talking about his child’s serious illness and measured how distressed the students felt afterward. They found that people with the AA or AC genotypes with A-alleles reported feeling much more upset and overwhelmed than those with the CC genotype Interestingly, while women in the study generally felt more empathy than men, the CD38 gene difference mainly affected how much personal distress people felt—not their ability to empathize.

This suggests that people with the A-allele may have stronger emotional reactions during stressful moments, but they can also feel so overwhelmed that it’s harder for them to stay calm or support others. In people who are highly sensitive to stress, this emotional overload can also show up physically.

Can Stress Sensitivity Be Inherited?

Studies have found that genetics account for part of why some people are more sensitive to stress than others. If one or both parents are highly sensitive or struggle with stress-related conditions, their children may inherit some of these traits. However, it’s not just about the DNA. A parent’s behavior, emotional patterns, and how they manage stress can also shape how their child responds to stress. So, stress sensitivity results from a mix of inherited traits and learned behaviors.

What Are The Symptoms of High Stress Sensitivity?

People who are highly sensitive to stress may experience a range of emotional, physical, and behavioral symptoms:

Emotional symptoms: People who are highly sensitive to stress often struggle with strong emotional reactions. They may feel anxious, easily irritated, or experience sudden mood swings. Even small challenges can feel overwhelming to them. It can also be difficult for them to stay calm or think clearly when under pressure.
Physical symptoms: Stress doesn’t only affect emotions, it may show up in the body too. Sensitive individuals may experience frequent headaches, constant tiredness, or digestive issues like stomach pain or bloating. Their muscles might feel tight, especially in the neck, shoulders, or jaw. Some may also notice their heart beating faster when they feel stressed. These physical symptoms are the body’s way of reacting to ongoing tension and can sometimes make the person feel even worse.
Behavioral signs: Stress sensitivity may also affect how people behave. For example, they might avoid situations that could cause stress, even if it affects their daily life. It can become difficult for them to concentrate on tasks, and they may struggle to stay focused. Sleep problems are also common, such as trouble falling asleep or waking up often during the night.

How to Manage and Reduce Sensitivity to Stress

Lifestyle Changes

Managing stress sensitivity starts with daily habits. Simple lifestyle changes can help balance the nervous system and improve resilience:

Mindfulness, Meditation, and Yoga: Practicing mindfulness, meditation, or yoga can calm the mind and reduce emotional reactivity. These techniques help you stay present and manage stress more effectively.
Regular Physical Activity: Engaging in activities like walking, swimming, or dancing can improve mood and reduce stress. Exercise helps release endorphins, which support emotional balance.
Quality Sleep: Getting enough restful sleep is essential for mental and physical well-being. Poor sleep can increase stress sensitivity and make it harder to cope with challenges.
Balanced Diet: Eating a healthy, nutritious diet supports brain function and energy levels. A balanced diet can also help regulate mood and reduce the effects of stress.
Time in Nature: Spending time outdoors or in green spaces can lower stress hormones and improve overall mood. Even short breaks in nature can help you feel more relaxed.

Therapeutic Approaches

Therapy can also help people manage stress sensitivity. Options include:

Cognitive Behavioral Therapy: CBT helps identify and change unhelpful thought patterns. It teaches practical skills to better manage emotional reactions to stress.
Stress Management Techniques: Techniques like deep breathing, muscle relaxation, or guided imagery can quickly reduce stress symptoms and promote calmness.
Exposure Therapy: Exposure therapy gradually introduces stressful situations in a controlled way. This helps reduce avoidance behaviors and build emotional resilience.

References

The Genetic Roots of Gambling Tendency

Catherine on March 1, 2025

Disclaimer: This article is for informational purposes only and is not intended to diagnose any conditions. LifeDNA does not provide diagnostic services for any conditions mentioned in this or any other article.

While gambling is a common behavior, experienced by 70-90% of individuals at some point, the tendency to gamble, especially to engage in risky or compulsive behavior varies significantly among people. For most, gambling remains an activity as a sort of entertainment, but for some, the urge becomes a persistent pattern, which may lead to harmful outcomes.

This tendency is not purely a matter of choice but may be influenced both by genetics and environmental factors. By understanding these influences, we can better understand why certain individuals develop a higher tendency for gambling, learning on ways to manage this behavior before it leads to addiction.

You may also want to read: Genes and Gambles: Deciphering the Genetics of Risk-Taking

What Is Gambling Tendency?

Gambling tendency refers to a person’s inclination or predisposition to engage in gambling activities. While many people may try gambling occasionally without any lasting effects, some people feel a stronger urge to gamble more often or take bigger risks. This habit can slowly grow over time. It doesn’t always lead to addiction, but it can become a problem if it starts affecting someone’s everyday life, choices, or relationships.

Gambling tendency doesn’t mean someone has a gambling disorder, but it can be an early sign that a person is at higher risk of developing one. People with a high gambling tendency may gamble more often, take greater financial risks, or find it difficult to stop once they start. Recognizing this pattern early is important in preventing the possible development of a gambling problem.

Signs of Gambling Tendency

Gambling tendency may not always be obvious at first, especially if the person still appears to function well in other areas of life. However, there are several warning signs that may indicate a growing issue:

Difficulty Controlling Gambling Habits: One of the most common signs of gambling tendency is struggling to limit how often or how much one gambles. A person may plan to gamble only occasionally but ends up spending more time and money than intended. This difficulty in self-control can lead to a harmful cycle of repeated gambling.

Gambling Despite Negative Consequences: Even when gambling causes problems, such as financial stress, relationship strain, or loss of focus at work or school. A person with a gambling tendency may continue the behavior.

Using Gambling as an Emotional Coping Tool: People with a strong gambling tendency might use gambling as a way to escape from negative emotions. Whether feeling sad, bored, anxious, or lonely, gambling may provide temporary relief or distraction. Over time, this habit can become a substitute for healthy emotional coping skills.

Financial Problems and Lying About Gambling: As gambling becomes more frequent, it can start to affect a person’s financial health. They may borrow money, miss bills, or even hide gambling losses from loved ones. Lying about gambling habits is a serious red flag that the tendency has become problematic and potentially harmful.

Preoccupation with Gambling: Constantly thinking about gambling, such as reliving past wins, planning the next session, or searching for betting opportunities.

You may want to read: Our Need For Instant Gratification May Be Genetic

What Causes Gambling Tendency?

Gambling tendency is not caused by one single reason, but rather a combination of influences that affect how a person responds to gambling opportunities. It may arise from a mix of genetic, psychological, environmental, and social factors.

Environmental and Social Influences

Growing up in an environment where gambling is normalized—such as having family members who frequently gamble can shape attitudes and increase gambling tendencies. Additionally, peer pressure, easy access to casinos or online betting platforms, and frequent exposure to gambling ads can make it more likely that someone will start gambling and continue doing so more often.

Life Circumstances and Stress

Stressful life events, financial pressure, or lack of social support can also push individuals toward gambling as an escape. In these cases, gambling tendency can develop as a coping mechanism rather than for entertainment, increasing the risk of long-term problems.

Heritability of Gambling Tendency

In exploring the genetic and environmental factors that shape gambling behaviors, twin studies have produced a wide range of results. Some studies suggest that genetic factors are the primary influence, with estimates showing that genetics may account for as much as 70% of gambling tendencies. The twin studies looked at in this review used twin studies to compare gambling behaviors between identical twins and non-identical twins. By comparing these two groups, researchers can figure out how much of gambling behavior is influenced by genetics, with a higher similarity in gambling habits between identical twins showing a stronger genetic influence.

The findings revealed that disordered gambling, which is a more serious form of gambling, is more strongly influenced by genetics (53%) compared to general gambling behaviors, which are more influenced by environmental factors (41%).

It also highlights how age and sex may impact these influences. In younger people, environmental factors, like peer pressure or family influences, were found to have a bigger effect on gambling behavior, while older individuals showed a stronger genetic influence. Additionally, the study found that men’s gambling behavior was more strongly linked to genetics (47%), while women’s behavior was more affected by environmental factors (14%).

These results suggest that genetic predispositions may make individuals more likely to gamble, but external factors, such as social influences, are also important, especially for women and younger people. The study emphasizes the importance of considering both genetic and environmental factors in understanding and addressing gambling behavior, as well as the need to consider age and sex when developing interventions.

Another study shows that genetics play an important role in gambling behavior, especially as people grow older. At age 18, genetic factors only accounted for about 21% of gambling tendencies, but by age 25, this increased to 57%. This suggests that as young adults gain more independence, the influence of their genetic makeup on their gambling behavior becomes stronger. In other words, as individuals transition from adolescence to adulthood, their inherited traits start to have a bigger impact on whether or not they gamble.

Another important finding from the study is that the genetic influence alone on gambling is consistent over time. The study found a moderate correlation between the genetic factors influencing gambling at age 18 and age 25, meaning that the same genetic traits are likely contributing to gambling behaviors throughout this period. This supports the idea that gambling tendencies are partly inherited, and these genetic factors remain stable as people grow older and gain more opportunities to gamble. This highlights the role of genetics in shaping who is more likely to develop gambling behaviors over time.

Are There Prevention or Treatment Options?

Yes, gambling tendencies may be managed and even prevented from progressing into a more serious issue. By recognizing the early signs and understanding the underlying causes, including genetics, people can take steps to protect themselves or help others.

Preventive Strategies

Learning about gambling tendency and its risks can help individuals make more informed choices. This includes understanding the odds of winning and the psychological tricks used in gambling environments. Limiting how often or how much you gamble, setting time and money limits, and avoiding high-risk environments can help prevent gambling from becoming a habit.

Behavioral Therapy

Cognitive Behavioral Therapy (CBT) is one of the most effective treatments for gambling tendencies and gambling disorders. CBT helps people understand the thoughts and feelings that drive their behavior, challenge irrational beliefs about winning, and learn healthier habits.

Support Groups and Counseling

Joining support groups like Gamblers Anonymous or seeking one-on-one counseling can be extremely helpful. Talking with others who have faced similar challenges can provide insight, encouragement, and accountability. Licensed therapists can also work with individuals to address underlying issues like anxiety, depression, or trauma that may contribute to gambling tendencies.

With proper education, support, and treatment, it is possible to manage gambling tendencies and avoid its more serious consequences. Whether you’re concerned about yourself or someone else, understanding the nature of this tendency is the first step toward a healthier relationship with gambling.

About the LifeDNA Personality and Cognition Report

Do you wonder why you might be more drawn to high-stakes situations or find it hard to resist the thrill of gambling?

Gambling behavior can have a genetic aspect, with genes influencing reward and risk-taking behaviors, particularly those within the dopamine pathways. A large-scale 2012 GWAS analyzed 2.38 million SNPs and identified six promising genetic variants across three genes : MT1X, ATXN1, and VLDLR that may play a role in gambling tendencies. These findings are part of LifeDNA’s Personality and Cognition Report, which sheds light on how your genes might influence impulsive or high-risk behaviors.

The Personality and Cognition Report from LifeDNA offers science-backed insights into how your DNA can shape behaviors like risk-taking, reward sensitivity, and impulse control. This report includes a detailed analysis of your genetic predisposition, helping you better understand the biological factors that may influence your choices.

References

Understanding the LifeDNA Methyl Plus Supplement

Catherine on February 16, 2025

What Is Methylation And What Does it Mean for Your Body?

Methylation refers to a complex series of biochemical reactions involving various enzymes and targets that are methylated (such as proteins, amino acids, DNA, and RNA) by the addition of a methyl group. The Methylation Cycle is one of the critical biochemical processes that actively uses methylation to modify amino acid and protein targets. This foundational understanding will enhance our exploration of how these genes influence the methylation cycle as well as their role in the various aspects of health and disease.

One of the important functions of the methylation cycle is the conversion of excess homocysteine (an amino acid) to methionine by the enzyme methionine synthase. This reaction requires methylcobalamin (a form of vitamin B12) and 5-methyltetrahydrofolate (produced from folate by the enzyme MTHFR).

Read about the Genetics of Methylation Cycle in more depth here.

Why Is It Important to Keep Homocysteine Levels in Check?

Homocysteine levels are significant because elevated levels of homocysteine, a sulfur-containing amino acid, are associated with an increased risk of cardiovascular diseases, including coronary artery disease, stroke, and peripheral arterial disease. High blood homocysteine levels can damage the lining of arteries, promote blood clot formation, and increase oxidative stress, all of which contribute to the development and progression of atherosclerosis.

About Methyl+

Methylation is a fundamental biochemical process in the body, influencing, for example, neurotransmitter production and cardiovascular health. It plays a crucial role in maintaining balance and overall well-being. Yet various factors, including genetics, diet, and lifestyle, can impact its efficiency.

To support optimal methylation, the body needs key nutrients that serve as methyl donors or co-factors in these processes. Methyl-Folate (5-MTHF), the biologically active form of folate, is a methyl donor and is essential for neurotransmitter function and mood regulation. Methylcobalamin, also a methyl donor, is known to be important for nerve function, and it contributes to energy metabolism. Vitamin B6, a methylation cycle co-enzyme, plays a role in neurotransmitter synthesis and energy metabolism, while Trimethylglycine (TMG), a methyl donor, supports healthy homocysteine levels by converting it to methionine, while it also supports detoxification processes in the liver.

As for the other ingredients in Methyl+, Vitamin K helps support calcium regulation for bone and heart well-being, Magnesium may help support muscle relaxation and the nervous system, and Vitamin D and Manganese play a role in bone well-being and immune function.

Ensuring sufficient intake of these nutrients can help optimize your genetic potential. Understanding the impact of maintaining proper methylation and how targeted nutrition supports this process can empower individuals to make informed choices about their health.

What Is In the Methyl+ Product?

Vitamin D (as Cholecalciferol)	125mcg
Vitamin K (as Menaquinone-7)	100mcg
Riboflavin (as Riboflavin-5-Phosphate)	15mg
Vitamin B6 (as Pyridoxal-5-Phosphate)	25mg
Methyl-Folate (as 5-Methyltetrahydrofolate)	5mg
Vitamin B12 (500 mcg as Methylcobalamin and 500 mcg as Adenosylcobalamin)	1000mcg
Magnesium (as Magnesium Citrate)	144mg
Manganese (as Manganese Citrate)	8mg
Trimethylglycine Betaine Base Anhydrous	650mg

Here are more details of each ingredient and their role in supporting the methylation cycle and well-being in general.

Vitamin D (as Cholecalciferol)
Primarily associated with bone health and immune function, Vitamin D.

Vitamin K (as Menaquinone-7)
Known for its role in blood clotting and bone metabolism, Vitamin K can support overall protein function and metabolism.

Riboflavin (as Riboflavin-5-Phosphate)
A vitamin that contributes to energy production and supports cellular function.

Vitamin B6 (as Pyridoxal-5-Phosphate)
This coenzyme aids in homocysteine metabolism and the transsulfuration pathway. By helping keep homocysteine in check, it supports the availability of methyl donors for use in protein methylation.

Methyl-Folate (as 5-Methyltetrahydrofolate)
5-MTHF directly provides methyl groups for the regeneration of methionine from homocysteine. This is critical for forming S-adenosylmethionine (SAM), the universal methyl donor for protein methylation.

Vitamin B12 (Methylcobalamin & Adenosylcobalamin)
Vitamin B12 is a key cofactor for methionine synthase, which recycles homocysteine back to methionine.

Magnesium (as Magnesium Citrate)
Magnesium is a cofactor in over 300 enzymatic reactions, including those that generate energy (ATP).

Manganese (as Manganese Citrate)
Manganese supports various enzyme functions and helps maintain general cellular health.

Trimethylglycine (Betaine Base Anhydrous)
Betaine serves as a methyl donor for the betaine-homocysteine methyltransferase pathway, which converts homocysteine to methionine.

Who Can Benefit from Methyl+?

Methyl+ may be beneficial for individuals looking to support cognitive function, cardiovascular health, and overall cellular well-being. It can be particularly useful for those with genetic variations affecting the methylation cycle (such as MTHFR variations), individuals with increased nutritional demands due to stress or lifestyle factors, and those seeking to optimize neurotransmitter balance and mood stability.

People with cardiovascular concerns, bone and joint health considerations, or those following restricted diets that may limit intake of essential methylation-supporting nutrients could also benefit from supplementation. As methylation cycle efficiency varies among individuals, consulting a healthcare professional can help determine if Methyl+ aligns with personal health needs.

Can you take Methyl+ if you are Pregnant?

Since prenatal nutrition is highly individualized, pregnant women should consult their healthcare provider before taking Methyl+. A doctor can ensure that the dosage and combination of nutrients align with their specific needs and do not exceed safe levels alongside other prenatal vitamins.

For further queries you can write to [email protected]

Grab a bottle of LifeDNA’s Methyl+ here.

References

Role of the BPIFB4 Gene in Longevity

Catherine on February 14, 2025

Aging is an incredibly complex phenomenon. It’s driven by a mix of genetic factors, the gradual buildup of wear-and-tear in our cells, and everyday choices about diet, exercise, and how we handle stress. More important than simply living longer is making sure those added years are fulfilling and vibrant. That’s why researchers and health professionals are focusing on “healthspan,” the length of time we stay healthy, rather than just the total number of years we’re alive.

By digging into the biology of aging, supporting public health initiatives, and encouraging personal lifestyle changes, we can potentially delay many of the health issues that come with getting older. The payoff? A better chance at remaining active, independent, and enjoying life well into our later years.

Would you like to understand your age-related genes in more depth? Check out LifeDNA’s Aging Report.

The BPIFB4 Gene

BPIFB4 (short for BPI fold-containing family B member 4) is a human gene that encodes a protein belonging to a group known as the BPI fold-containing family. The “BPI fold-–containing family” is a group of proteins that share a specific three-dimensional shape known as the BPI fold.

The letters “BPI” stand for “bactericidal/permeability-increasing,” referring to proteins that can bind and neutralize bacterial components, helping the immune system fight infections. Since the family of proteins that have this structural fold tend to share functional similarities in immune response and inflammation control, they are grouped under this umbrella term.

The Longevity-Associated Variant

The Longevity-Associated Variant (LAV-BPIFB4) is a specific version of the BPIFB4 gene that has been linked to healthier aging and a longer lifespan. Researchers found this variant more often in people who live to very old ages, such as centenarians. It appears to have protective effects on the body, especially in maintaining cardiovascular health and reducing inflammation.

Several aspects of aging and longevity are tied to LAV-BPIFB4:

Vascular Health

An aging heart gradually loses function, and current treatments cannot fully prevent this decline. Some individuals maintain heart health into old age due to beneficial genetic factors, including the LAV of BPIFB4.

A 2023 study showed that LAV-BPIFB4 carriers experience fewer cardiovascular issues. Delivering this gene via gene therapy improves heart function in disease models. In elderly patients with heart failure, pericytes (cells supporting blood vessels) are significantly reduced. However, this defect was less severe in those with the LAV-BPIFB4 genotype. Supplementing with LAV-BPIFB4 restored pericyte function, improved blood vessel support, and prevented heart deterioration in mice. These findings suggest that LAV-BPIFB4 could be a promising therapy to slow or reverse heart aging.

A 2021 study showed that LAV-BPIFB4 plays a crucial role in protecting the heart by supporting key enzymes like eNOS and PKC-alpha.

eNOS (endothelial nitric oxide synthase) is an enzyme that produces nitric oxide (NO), a molecule that helps relax blood vessels and improve circulation.
PKC-alpha (Protein Kinase C-alpha) is an enzyme that plays a role in regulating functions like blood vessel tone, inflammation, and heart muscle contraction.

LAV-BPIFB4 therapy also restores immune balance by lowering inflammation and enhancing protective factors, mimicking the natural advantages seen in long-lived individuals. These findings suggest that LAV-BPIFB4 could be an important target for treating cardiovascular diseases and promoting healthy aging.

Understand the Genetics of Vascular Aging in more depth

Inflammation

Inflammation plays a crucial role in longevity because chronic low-grade inflammation, often called “inflammaging,” is a key driver of aging and many age-related diseases. While short-term inflammation helps the body fight infections and heal injuries, persistent inflammation over time can damage tissues, accelerate cellular aging, and increase the risk of conditions such ascardiovascular disease, diabetes, neurodegeneration, and cancer.

Read our deep dive analysis of the “Genetics of Inflammatory Response”

Long-lived individuals, such as centenarians, tend to have better-regulated immune responses with lower levels of chronic inflammation and higher levels of anti-inflammatory factors. According to a 2023 study, centenarians exhibit a unique immune profile characterized by higher levels of both pro-inflammatory and certain regulatory cytokines compared to middle-aged individuals. While markers of inflammation such as TNF-α, IL-6, IFN-α, and IL-23 were elevated, the study also found an increase in IL-19, a cytokine that shifts immune responses toward a less inflammatory state.

The immune systems of centenarians remain more balanced, allowing them to fight infections effectively without excessive inflammatory damage. Research suggests that gene variants linked to longevity, such as LAV-BPIFB4, may help control inflammation by modulating immune system activity and reducing harmful inflammatory markers.

Lifestyle factors also play a major role in controlling inflammation. A healthy diet (rich in antioxidants and healthy fats), regular exercise, stress management, and good sleep habits can all help keep inflammation in check, supporting longer and healthier lives.

Ultimately, reducing chronic inflammation is a key strategy for improving healthspan, the number of years a person remains healthy and functional.

In an article published in 2024, researchers used a high-throughput proteomic approach to analyze circulating proteins in 591 participants from the PLIC cohort based on their BPIFB4 genotype. The study found that individuals with homozygous LAV-BPIFB4 had lower levels of immune-inflammatory markers compared to those with other BPIFB4 variants. Further in vitro experiments on intestinal epithelial tissues from inflammatory bowel disease (IBD) patients showed that LAV-BPIFB4 treatment had beneficial effects, suggesting its potential role in improving intestinal health and immune regulation.

Scientists are still exploring ways to use LAV-BPIFB4 in medicine, including using it via gene therapy and small molecules that could mimic its effects. While the research is still in the early stages, this variant could one day help people stay healthier for a longer time.

Summary

The BPIFB4 gene, particularly its Longevity-Associated Variant (LAV-BPIFB4), is linked to healthier aging by supporting heart function, reducing inflammation, and improving immune balance. Found more often in centenarians, this variant enhances vascular health by boosting nitric oxide production and protecting blood vessels. Research shows it may help prevent age-related diseases and has potential for gene therapy. Studies have also found that those with LAV-BPIFB4, with lab tests suggesting benefits for intestinal health. While still in the early stages, LAV-BPIFB4 could be key to extending healthspan and delaying aging-related decline.

References

Rare Genetic Conditions: Pyruvate Dehydrogenase Deficiency

Catherine on February 13, 2025

Pyruvate Dehydrogenase Deficiency (PDD) is a rare genetic disorder that affects the body’s ability to convert pyruvate into acetyl-CoA, a key molecule in cellular energy production. Around 1 in 50,000 births in the USA are affected by PDD.

This condition leads to the accumulation of lactic acid in the blood (lactic acidosis) and impaired energy metabolism. This primarily affects the brain and nervous system. Understanding the genetic basis of PDD is essential for diagnosis, management, and potential treatment strategies.

The Role of the Pyruvate Dehydrogenase Complex (PDC)

The Pyruvate Dehydrogenase Complex (PDC) is a multi-enzyme structure. Its role is to hasten the conversion of pyruvate into acetyl-CoA, which then enters the Krebs cycle to make ATP.

When food enters your body it is instantly welcomed by hundreds of biochemical processes happening in tandem. One of these processes is called glycolysis. During glycolysis, the carbohydrates are broken down to their simplest form, a sugar called glucose. Once glucose is made, it needs to be processed in a way that is compatible for it’s use in another chain of biochemical reactions called Kreb’s cycle (also known as the Citric Acid Cycle). Kreb’s cycle is ultimately responsible for making energy that cells can use (through ATP).

This is where pyruvate plays an important role. Pyruvate turning into acetyl-CoA is like a bridge. Through this process the products of sugar breakdown (glycolysis) are prepared for the cell’s main energy factory (the Kreb’s cycle).

In simple terms, once glucose is split into 2 pyruvates, these are transformed into acetyl-CoA so that they can enter the cycle that churns out lots of ATP (the cell’s energy currency).

If this conversion doesn’t happen, the cell can’t fully capture the energy stored in glucose.

Let’s take a look at PDC in more depth to understand the genetic impact in upcoming sections better.

The PDC consists of three primary enzyme components:

E1 enzyme (Pyruvate Dehydrogenase, PDH) – Encoded by the PDHA1 gene, this enzyme catalyzes the first step of the reaction.
E2 enzyme (Dihydrolipoamide Acetyltransferase) – Encoded by the DLAT gene, this enzyme facilitates the transfer of acetyl groups.
E3 enzyme (Dihydrolipoamide Dehydrogenase) – Encoded by the DLD gene, it helps regenerate cofactors required for continued enzymatic function.

PDC also includes regulatory proteins such as PDHX, PDP1, and PDPR, which help control enzyme activity. Mutations in any of these genes can lead to PDD, with PDHA1 mutations being the most common cause.

Genetic Basis of Pyruvate Dehydrogenase Deficiency

PDD is primarily caused by mutations in the PDHA1 gene, located on the X chromosome. Since PDHA1 is X-linked, the inheritance pattern differs between males and females:

Males (XY): A single mutation in PDHA1 typically results in full disease expression, as they lack a second X chromosome to compensate.
Females (XX): Due to X-inactivation, the severity of symptoms can vary. Some females may have mild or even asymptomatic cases, while others experience significant neurological impairment.

While X-linked PDD is the most common form, mutations in autosomal genes like PDHX, DLAT, and DLD follow an autosomal recessive inheritance pattern. In these cases, an individual must inherit two defective copies (one from each parent) to develop the disorder.

Symptoms and Clinical Presentation

PDD primarily affects energy-demanding tissues, such as the brain, muscles, and heart. Symptoms vary in severity but commonly include:

Neurological issues – Developmental delay, poor muscle tone, seizures, and ataxia (lack of coordination).
Lactic acidosis – Buildup of lactic acid in the blood, leading to fatigue, vomiting, and difficulty breathing.
Intellectual disability – Ranges from mild to severe, depending on the mutation and residual PDC activity.
Growth failure – Delayed physical development due to energy deficits.

Diagnosis and Genetic Testing

Diagnosing PDD involves a combination of biochemical tests and genetic analysis:

Blood and CSF Tests – Elevated lactate and pyruvate levels suggest metabolic dysfunction.
Enzyme Activity Assay – Measures the activity of PDC in white blood cells, muscle tissue, or fibroblasts.
Genetic Testing – Identifies specific mutations in PDHA1 or other related genes, confirming the diagnosis and aiding in family planning.

Management and Treatment

There is no cure for PDD, but treatment focuses on managing symptoms and optimizing metabolic function:

Ketogenic Diet

High-fat, low-carb diets help bypass the need for a functional Pyruvate Dehydrogenase Complex (PDC) by using ketones as an alternative energy source.

In a 2017 study, nineteen patients, mostly with prenatal-onset disease, were treated with a ketogenic diet for a median of 2.9 years. The diet improved symptoms such as epilepsy, ataxia, sleep, speech, and social function, and reduced hospitalizations, though with one patient having to stop the intervention due to pancreatitis. Poor diet adherence led to relapsing ataxia and stalled development.

Other Methods

Thiamine Supplementation

Some patients respond to high-dose vitamin B1 (thiamine), a cofactor of PDC.

A case report published in 2022, describes a 2-year-old Japanese boy with a novel PDHA1 gene mutation (p.T111I) and thiamine-responsive PDHC deficiency. He experienced recurrent episodes of muscle weakness, ataxia, and elevated lactate levels. Initial treatments with standard thiamine doses were ineffective, but higher doses (up to 1,000 mg/day) improved symptoms. Long-term thiamine therapy stabilized his condition, with no attacks for 18 months (during the study period).

Dichloroacetate (DCA)

This experimental drug helps reduce lactic acidosis by stimulating pyruvate dehydrogenase phosphatase.

Supportive Care

Physical therapy, speech therapy, and anticonvulsant medications help manage symptoms.

Conclusion

Pyruvate dehydrogenase deficiency is a complex genetic disorder that severely impacts energy metabolism, primarily affecting the nervous system. Understanding the genetic mutations involved, particularly in PDHA1, is key to accurate diagnosis and personalized treatment strategies. Advances in metabolic therapy and genetic research may pave the way for more effective treatments in the future, offering hope to individuals affected by this rare but debilitating condition.

References

A Deep-Dive on the Genetics of NOS3 & Heart Health

Catherine on February 12, 2025

What is NOS3?

Nitric oxide is a gas produced by the body, made from equal parts oxygen and nitrogen. Its primary job is to relax the blood vessels, allowing more blood, oxygen, and nutrients to flow to vital organs. This helps keep your heart and blood vessels healthy.

NOS3, or nitric oxide synthase 3, is an important enzyme in the body that helps produce nitric oxide. It is especially active in the blood vessels and the heart. NOS3 can be thought of as a “factory” inside the body, making nitric oxide to ensure smooth blood flow and proper heart function. The role of nitric oxide is protecting the endothelium, the thin layer of cells that line the inside of blood vessels. If the body doesn’t make enough nitric oxide, the endothelium may become damaged which may increase the risk of cardiovascular disease.

Why is Nitric Oxide Important?

Nitric oxide or NO has several key jobs in the body, especially in the cardiovascular system (the heart and blood vessels). One of the main things NO does is to help relax the muscles in your blood vessel walls. When the blood vessel walls relax, they open up, allowing blood to flow more easily and reducing blood pressure. This helps maintain healthy circulation and prevents the heart from having to work too hard.

NO also has a protective effect by preventing the formation of clots inside the blood vessels. It stops platelets, the small cells that form clots, from sticking together, which lowers the risk of dangerous blockages. Additionally, NO keeps immune cells from sticking to the blood vessel walls, which is important for preventing inflammation and damage.

What Happens if NOS3 Doesn’t Work Right?

If the NOS3 enzyme doesn’t work properly, your body might not produce enough nitric oxide. This may lead to several problems, such as high blood pressure (because your blood vessels don’t relax as they should) and an increased risk of heart disease. There are also specific changes in the NOS3 gene that may affect how well it works, and these changes are linked to a higher risk of heart problems.

There are several genetic variations (known as SNPs or single nucleotide polymorphisms) in the NOS3 gene that can impact its function:

rs1800779 (G51-898A): This genetic variation has been linked to higher cardiovascular risk markers, including increased blood pressure. People with the risk ‘G’ allele may have reduced NOS3 expression or activity, leading to lower nitric oxide production and increased blood pressure.
rs1799983 (T894G): Another common SNP in the NOS3 gene, this variation has also been associated with cardiovascular health issues. Like the G51-898A variant, it may affect the enzyme’s ability to produce nitric oxide properly.
rs1800783 (A-52+1009T): This SNP has also been studied for its role in cardiovascular health, and like the other NOS3 gene variations, it may influence nitric oxide production and increase the risk of heart disease.

NOS3 and Heart Health

A study explored how genetic variations in the NOS3 gene, which plays a role in blood vessel function by producing nitric oxide, may influence the risk of heart problems and the effectiveness of certain medications. One particular variation in the NOS3 gene, -690 C>T (rs3918226), was associated with a slightly increased risk of coronary heart disease (CHD), a condition where the blood vessels supplying the heart become clogged. On the other hand , the -922 A>G (rs1800779), was linked to a slightly higher risk of heart failure, a condition in which the heart struggles to pump blood effectively.

The study also tested how three different blood pressure medications—amlodipine, lisinopril, and chlorthalidone—worked in people with these genetic variations. They found that for individuals with the -690 C>T variation, amlodipine was more effective than lisinopril at reducing the risk of stroke. For those with the Glu298Asp G>T(rs1799983) variation, taking amlodipine was linked to a lower risk of dying from any cause compared to those who took lisinopril.

The study suggests that genetic information may help doctors make better medication choices for patients, potentially reducing the risk of serious heart problems and improving health outcomes.

NOS3 Gene Variations and Smoking in Heart Disease

Recent research has explored how smoking might influence the connection between variations in the NOS3 gene and the risk of developing coronary heart disease (CHD) and ischemic stroke. The NOS3 gene plays a crucial role in producing an enzyme that helps keep blood vessels healthy. When there are genetic variations in this gene, it may affect blood vessel function, potentially increasing the risk of cardiovascular diseases.

The study involved 1,085 individuals with incident CHD, 300 with ischemic stroke, and 1,065 healthy participants. The researchers focused on two additional specific genetic variations in NOS3: the T-786C (rs2070744) and E298D (rs1799983) polymorphisms. They examined how these variations interacted with smoking history to affect the risk of heart disease and stroke.

The study found that the risk of CHD was higher in smokers carrying the E298D variant of the NOS3 gene. Specifically, smokers with the D298 allele were more than twice as likely to develop CHD compared to nonsmokers who carried two “normal” E298 alleles. This highlights the heightened risk of cardiovascular disease for smokers with this specific genetic variant.

In African-Americans, the T-786C genetic variation was associated with an increased risk of ischemic stroke, especially in individuals who had a long history of smoking (20 or more pack-years). Smokers carrying the C-786 allele were at a significantly higher risk of stroke than those with fewer smoking years or nonsmokers.

This suggests that both smoking and certain genetic variations in the NOS3 gene may add up together to increase the risk of developing heart disease and stroke. The findings highlight the importance of considering both genetic factors and environmental factors like smoking when assessing cardiovascular health risk. Understanding how these factors interact could help in identifying individuals at higher risk and tailoring preventive measures more effectively.