Folic Acid and Genetic Factors Reduce Risk of Gestational Hypertension: Study
China: Researchers have discovered in a new study that pre-pregnancy folic acid intake, along with favorable genetic factors, is associated with a lower risk of gestational hypertension. These findings highlight the important role of pre-pregnancy nutrition and genetic predisposition in reducing the risk of hypertension during pregnancy.
A new prospective cohort and epigenome-wide association study published in the European Journal of Preventive Cardiology by Wei Zheng from the Department of Clinical Nutrition, Capital Medical University, Beijing, and colleagues sheds light on the complex interplay between folic acid intake, genetic variations, and DNA methylation in hypertensive disorders of pregnancy (HDP). The study addresses long-standing inconsistencies in research on folate levels and pregnancy-related hypertension by incorporating genetic and epigenetic perspectives.
For this purpose, the researchers followed a cohort of 4,079 pregnant women in China between 2022 and 2024, examining the relationship between folic acid intake, genetic polymorphisms involved in folate metabolism, and red blood cell (RBC) folate metabolites and the risk of gestational hypertension and preeclampsia. To further explore epigenetic mechanisms, the team conducted an epigenome-wide association study using data from 231,057 women in the UK Biobank.
The key findings were as follows:
- 4.8% of participants developed gestational hypertension, while 4.4% experienced preeclampsia.
- Persistently low levels of RBC 5-methyltetrahydrofolate (the active form of folate) were associated with a 57% higher risk of gestational hypertension compared to median levels.
- Higher levels of unmetabolized and intermediary folate metabolites were linked to more than a twofold increase in the risk of gestational hypertension.
- Pre-pregnancy folic acid intake was associated with increased levels of both active folate and intermediate metabolites.
- Pre-pregnancy folic acid intake showed an overall protective association against gestational hypertension.
- Genetic variants associated with lower active folate levels and higher unmetabolized metabolites were linked to an increased risk of gestational hypertension.
- Two DNA methylation sites, cg16489826 and cg17054900, were significantly associated with hypertensive disorders of pregnancy.
These findings indicate that folate-related DNA methylation changes may play a role in the development of hypertensive disorders during pregnancy.
Overall, the study highlights that both nutritional and genetic factors influence HDP risk through their effects on folate metabolism. It also points to a potential role for epigenetic regulation in mediating these associations. These findings may help inform future strategies for early risk assessment and targeted prevention of hypertensive complications during pregnancy.
Reference:
Zheng, W., Yang, R., Lu, Y., Yuan, X., Zhang, Y., Yan, X., Zhang, L., Huang, J., Pang, H., Zhang, P., Chen, T., & Li, G. Folic Acid Intake, Genetic Variations, and DNA Methylation in Hypertensive Disorders of Pregnancy : A Prospective Cohort and Epigenome-Wide Association Study. European Journal of Preventive Cardiology. https://doi.org/10.1093/eurjpc/zwag186
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