Methylenetetrahydrofolate Reductase Polymorphisms and the Risk of Gestational Hypertension

Background: Evidence on the association of 5,10 methylentetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms in women with gestational hypertension is inconsistent. It is also unknown whether the fetal genotype is relevant, or whether folic acid supplementation modifies this association. Methods: The study population was composed of U.S. and Canadian white women with nonmalformed infants participating in the Slone Epidemiology Center Birth Defects Study between 1993 and 2000. Women were interviewed within 6 months after delivery regarding multivitamin use in pregnancy and the occurrence of gestational hypertension, among other factors. DNA was extracted from cheek swabs and gene alleles determined by restriction fragment length polymorphism analysis. We compared the prevalence of the 677TT/CT and 1298CC/AC genotypes between cases with gestational hypertension (54 mothers and their 51 offspring) and controls (100 mothers and their 99 offspring). We also estimated odds ratios (ORs) and 95% confidence intervals (CIs) using conditional logistic regression to control for geographic region and calendar year. Results: The T allele was present in 69% of women with gestational hypertension versus 57% of control women (compared with 677CC, OR = 1.9; 95% CI = 0.9–4.0). The offspring of case and control women had a 677TT/CT genotype prevalence of 68% and 47%, respectively (2.4; 1.1–5.0). Among women supplemented with folic acid during the first 5 months of pregnancy, the ORs for maternal and fetal 677TT/CT genotypes were 0.9 (0.3–2.5) and 2.1 (0.7–6.0), respectively. Neither maternal nor fetal 1298CC/AC genotypes were associated with an increased risk of gestational hypertension. Conclusion: Maternal and fetal MTHFR C677T polymorphism may be associated with a moderately increased risk of gestational hypertension, and there is a suggestion that this association may be diminished among women receiving folate supplementation during pregnancy.

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