The COMT (Catechol-O-Methyltransferase) gene is essential in the metabolic pathway that breaks down catecholamines. Catecholamines are a group of neurotransmitters, including dopamine, epinephrine, and norepinephrine. These neurotransmitters play vital roles in the brain’s functioning and impact mood, stress response, and cognition.Â
The COMT enzyme, encoded by the COMT gene, is particularly active in the prefrontal cortex, a brain region associated with memory, decision-making, and emotional regulation. Genetic variations in the COMT gene can affect the enzyme’s activity level, influencing how quickly catecholamines are metabolized. This can directly impact neurological and psychological processes.
The most studied COMT polymorphism is Val158Met (rs4680 G>A), which results from a substitution of amino acids valine (Val) with methionine (Met) at codon 158 of the enzyme (protein). This polymorphism significantly influences the enzyme’s activity: the Met variant exhibits a three to four times lower enzymatic activity than the Val variant.Â
As a result, individuals with the Met/Met genotype (rs4680 AA) break down dopamine more slowly than those with the Val/Val genotype (rs4680 GG), affecting various aspects of cognition and emotional regulation.
COMT polymorphisms, particularly Val158Met (rs4680 G>A), have been linked to several aspects of health and wellness. The slower dopamine metabolism in Met variant carriers (rs4580 GA or AA) can impact cognitive functions, such as working memory and attention, and contribute to differences in pain sensitivity and stress resilience.Â
Additionally, variations in the COMT gene are associated with psychiatric disorders, including anxiety, depression, and schizophrenia. It’s important to remember that these relationships are complex and influenced by environmental factors. The gene’s influence on estrogen metabolism suggests a role in conditions like fibroids and certain cancers.
An early 2005 study involving 497 undergraduate students found that two SNPs (rs4680 and rs737865) of the COMT gene were significantly associated with lower levels of extraversion. And, to a lesser extent, higher levels of neuroticism, particularly in women.Â
A 2015 study involving 753 healthy participants revealed that individuals with the A-allele of rs4680 or the T-allele of rs4633 demonstrated significantly better performance in insight problem-solving. Additionally, the interaction between the COMT gene’s rs5993883 SNP and gender was significant in determining the success in solving insight problems, notably showing an effect exclusively in males.
A 2020 study aimed to explore how genetic factors influence the effectiveness of working memory training. Data from the 30 participants who underwent adaptive training in a randomized controlled trial (RCT) were combined with data from an additional 71 participants who received the same training outside of the RCT (a total of 101 participants). The study revealed that individuals with the Met(A)allele of Val158/108Met experienced a more significant decrease in brain activation in the left prefrontal cortex post-training than those with the Val-allele homozygotes (rs4680 GG). A decline in brain activation, particularly in a region as crucial as the left prefrontal cortex, often indicates an increase in neural efficiency.
A 2021 study investigated the role of genetic factors in memory performance, focusing on variants in two significant dopaminergic neurotransmission genes, COMT (SNP rs4680) and Brain-derived neurotrophic factor (BDNF) (SNP rs6265). These genes are associated with memory abilities. After analyzing two independent general population cohorts totaling 5,937 individuals, the findings revealed significant two-way interactions between COMT and BDNF in both cohorts without any direct genetic effects. Further sensitivity analyses indicated that these interactions were predominantly evident in females.Â
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A 2011 study showed that the COMT rs165774 SNP was significantly associated with alcohol dependence. Further, the combined haplotype analysis of rs165774 and rs4680 underscored an association with alcohol dependence, with the G/G haplotype appearing more frequently in alcohol-dependent cases.Â
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A 2021 review of pharmacogenetic studies indicated a significant response to olanzapine in schizophrenia patients with the COMT rs4680 A-allele and rs4680-rs4818 CA haplotype. The review also detailed associations between the COMT rs4680 variant and antidepressant treatment efficacy. Furthermore, particular genotypes of the rs933271 variant were related to better outcomes in methadone maintenance treatment for opioid dependence.
*LifeDNA currently does not offer pharmacogenetic testing reports
A 2017 case-control study (143 patients) delved into the relationship between the COMT gene and Parkinson’s disease (PD) in Chinese patients. The study revealed that carriers of the rs4633 T-allele and/or rs4680 A-alleles and the combined rs4633-rs4680 T/A haplotype were significantly more prevalent in the early-onset PD group than in healthy controls. The findings suggest that the combination of functional COMT SNPs might influence the risk of PD, its progression, treatment response, and symptom severity.
According to another 2017 study, the frequency of the A-allele in the COMT rs4680 SNP was higher in PD patients with pain than those who were pain-free. Pain severity was notably associated with longer disease duration and the simultaneous presence of the COMT rs6267 T-allele. After stratifying PD patients by depression status, the association between the COMT rs6267 GT- genotype and pain severity persisted. Additionally, participants with the COMT rs4680-GG and GA genotypes reported higher pain severity than those with the AA genotype.
Checking for COMT polymorphisms typically involves genetic testing through saliva or blood samples. Many direct-to-consumer genetic testing services, like LifeDNA, offer insights into COMT status among their genetic analyses. These services analyze your DNA for specific polymorphisms, including the Val158Met, providing information about your genotype.Â
It is vital to choose a reputable company that ensures the accuracy and privacy of your genetic data. Additionally, genetic counseling can help interpret the results and understand their implications for your health and wellness.
The LifeDNA Methylation Genes Report is a specialized genetic analysis focused on COMT and related genes, like MTHFR. The MTHFR gene is well-known for its role in folate metabolism and other health-related conditions. The report also provides individuals with detailed insights into their specific COMT gene variants.
Understanding your COMT polymorphism status can provide valuable insights into your health and wellness, particularly regarding stress response, pain sensitivity, and potential risks for some conditions. However, it is crucial to remember that genetics is only one piece of the health puzzle. Environmental factors, lifestyle choices, and psychological well-being also play significant roles.Â
If you discover you carry a COMT polymorphism that may impact your health, consider discussing the findings with a healthcare provider or a genetic counselor. They can offer personalized advice on managing any associated risks and optimizing your health through lifestyle adjustments, stress management techniques, and, if necessary, medical interventions.
*Understanding your genetics can offer valuable insights into your well-being, but it is not deterministic. Your traits can be influenced by the complex interplay involving nature, lifestyle, family history, and others.
Our reports have not been evaluated by the Food and Drug Administration. The contents on our website and our reports are for informational purposes only, and are not intended to diagnose any medical condition, replace the advice of a healthcare professional, or provide any medical advice, diagnosis, or treatment. Consult with a healthcare professional before making any major lifestyle changes or if you have any other concerns about your results. The testimonials featured may have used more than one LifeDNA or LifeDNA vendors’ product or reports.
