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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.
Preeclampsia (PE) is a serious pregnancy complication characterized by the expecting mother’s high blood pressure and signs of organ damage, often affecting the liver and kidneys. It typically arises after 20 weeks of pregnancy and can lead to severe complications for both the mother and baby if left untreated.Â
Despite extensive research, the exact cause of preeclampsia remains unclear. However, increasing evidence suggests that genetic factors play a crucial role in its development.Â
This article explores the genetic underpinnings of preeclampsia, highlighting key genetic markers, inheritance patterns, and potential implications for future research and treatment.
Preeclampsia is considered a multifactorial disorder, influenced by both genetic and environmental factors. Studies have identified several genes and genetic variations associated with an increased risk of preeclampsia.
Research suggests that both maternal and fetal genes contribute to preeclampsia risk. The maternal genome influences how the mother’s body adapts to pregnancy, while fetal genes inherited from both parents affect placental function, which is crucial in preeclampsia development.
 In a 2020 study researchers identified placental genetic and epigenetic markers, notably the upregulation of the microRNA MIR138 in preeclamptic placentas of female infants.
Another 2020 study highlighted the role of the complement system in preeclampsia risk. The complement system is an important aspect of immune response. Researchers hypothesized that specific combinations of maternal and fetal complement gene SNPs can contribute to preeclampsia risk. Sequencing factor H (CFH), C3, and CD46 genes revealed nine common SNPs, with two fetal CD46 variants showing significantly higher frequencies in preeclampsia cases.
Several genes have been linked to preeclampsia (PE), including:
FLT1 (Fms-related tyrosine kinase 1) gene encodes a protein involved in making blood vessels. Increased levels of soluble FLT1 (sFLT1) are found in preeclamptic women. This leads to poor blood flow to the placenta.
In the same year, another study performed on the Japanese population also found elevated levels of FLT1 mRNA in women with preeclampsia. However, the authors note that a larger study is needed to definitively ascertain this link.
A 2023 RNA sequencing study flagged FLT1 as one of the genes whose expression was upregulated in African-American women with severe preeclampsia.
A 2020 study in Estonian cohorts observed the rs4769613-C variant to be associated with preeclampsia. This SNP is located in an enhancer near FLT1.. The study also notes that identifying this variant in cell-free fetal DNA (cffDNA) from maternal blood could aid in early risk assessment for preeclampsia.
ENG is another key gene in blood vessel function, and elevated levels of soluble endoglin contribute to endothelial dysfunction, a hallmark of preeclampsia. Elevated soluble endoglin (sEng) levels are found in the serum, plasma, and urine of preeclampsia patients. The sEng are generated through membrane-bound endoglin are broken away by metalloproteases (a kind of enzyme) and potentially other proteases. A study published in February of this year (2025) showed that thrombin could possibly be responsible for this. Thrombin is the key protein that helps your body in the clotting process.
A 2021 systematic review and meta-analysis of 20 studies involving 1146 preeclamptic and 1675 normotensive pregnant women found that soluble endoglin levels were significantly higher in preeclamptic women during the second and third trimesters. Elevated soluble endoglin levels were observed in both early-onset and late-onset preeclampsia.Â
A retrospective study, also published in 2021, was performed on 124 women to study the angiogenic and metabolic placental factors in type 1 diabetes, type 2 diabetes, gestational diabetes, preeclampsia, and control groups. The results showed that the genetic expression of the ENG gene was the highest in patients with preeclampsia.
The MTHFR gene, short for Methylenetetrahydrofolate Reductase, is crucial in the body’s metabolic processes. This gene is responsible for producing the MTHFR enzyme, which plays a vital role in processing amino acids, the building blocks of all proteins.Â
Read our in-depth analysis of the MTHFR gene here.
A 2020 case-control study examined the role of methylenetetrahydrofolate reductase (MTHFR), homocysteine, and MDA levels in 30 preeclampsia patients and 30 healthy pregnant women. Results showed significantly higher homocysteine and MDA levels in preeclamptic women, along with reduced MTHFR activity. This suggests impaired homocysteine metabolism. These findings highlight the role of homocysteine regulation and MTHFR activity in blood pressure control, making them potential targets for preeclampsia prevention and treatment.Â
A 2023 study investigated the role of polymorphisms in eNOS (-786 T > C, 894 G > T) and MTHFR (1298 A > C, 677 C > T)Â in preeclampsia among 160 patients and 160 healthy pregnant women in Quanzhou (Han population). Variants eNOS 894 G > T and MTHFR 1298 A > C showed no significant differences. However, the eNOS -786 C allele (OR: 2.07, p = 0.03) and MTHFR 677 T allele (OR: 1.83, p = 0.04) were more frequent in preeclampsia (PE) patients.Â
Additionally, women with the eNOS -786 CC genotype had lower nitric oxide (NO) levels, while those with the MTHFR 677 TT genotype had higher homocysteine (Hcy) levels, both of which contribute to vascular dysfunction in PE. These findings suggest that eNOS -786 CC and MTHFR 677 TT genotypes may serve as genetic predictors of PE risk.
Interestingly, however, a systematic review, also published in 2023, done on relevant case-control studies between 2000 and 2019, irrespective of ethnic background, showed no statistical significance between the MTHFR 677 T allele and preeclampsia risk.Â
Another case-controlled study comprising of women from South India showed that preeclampsia was common in women carrying the T variant of MTHFR rs1801133 SNP.Â
The AGT (angiotensinogen) gene, particularly the M235T variant, has been implicated in preeclampsia in some studies. But the association remains inconsistent across different populations.Â
Findings from a 2021 study suggest that AGT M235T polymorphism does not play a significant role in preeclampsia pathophysiology in the Thai population, despite previous associations with increased blood pressure in pregnancy. Similar findings were recorded in a 2022 study on the Chinese population.
Preeclampsia exhibits a strong familial component, with women having a higher risk of developing the condition if their mother or sister had preeclampsia.Â
Daughters of women with a history of preeclampsia are at an increased risk, indicating a hereditary predisposition.
Some studies suggest that a father’s genetic contribution may also play a role. Men born to preeclamptic mothers have a higher likelihood of fathering pregnancies affected by preeclampsia.
As seen in the previous sections, rather than a single gene, multiple genetic variants collectively contribute to susceptibility, making preeclampsia a polygenic disorder.
Epigenetic modifications, such as DNA methylation and histone modifications, regulate gene expression without altering the underlying genetic code. Environmental factors, including maternal diet, stress, and exposure to pollutants, can influence these epigenetic changes and potentially contribute to preeclampsia risk.
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Abnormal DNA methylation patterns in placental tissues of preeclamptic women can affect genes involved in angiogenesis and immune function. A 2020 epigenetic study showed higher ENG methylation in preeclampsia cases. But more robust studies are needed to establish this link definitively.Â
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MicroRNAs (small RNA molecules that regulate gene expression) show altered expression in preeclampsia, impacting placental function. A 2021 study investigated CD4+ T cells in preeclamptic and healthy pregnant women. Results showed that miRNA-326 was upregulated in CD4+ cells of women with preeclampsia. Similarly, findings from a 2020 study suggests that plasma exosomal miRNA profiling could enhance understanding of preeclampsia pathophysiology and serve as a potential diagnostic tool.
Understanding the genetic basis of preeclampsia has important clinical implications:
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Preeclampsia remains a major global health challenge, but advances in genetic research are shedding light on its complex origins. While no single gene is responsible for the condition, a combination of maternal, paternal, and fetal genetic factors contribute to its development. Further research, particularly in genomics and epigenetics, holds promise for improving early detection, prevention, and treatment strategies for preeclampsia, ultimately enhancing maternal and neonatal health.
