One-carbon metabolism enzyme polymorphisms and uteroplacental insufficiency

OBJECTIVES: This study was undertaken to test novel genetic polymorphisms involved in 1-carbon metabolism for a potential association with increased risk of developing pregnancy complications associated with uteroplacental insufficiency. STUDY DESIGN: This was a prospective cohort study consisting of 50 women at low risk and 93 women at high risk for having a pregnancy complication develop. Maternal and fetal DNA samples were genotyped for methionine synthase (MTR) A2756G, methionine synthase reductase (MTRR) A66G and methylenetetrahydrofolate dehydrogenase (MTHFD1) G1958A. A chi squared or chi(2) analysis was used to compare genotypes and pregnancy outcome, 1-way analysis of variance and linear regression were used to compare genotype with continuous variables. RESULTS: The fetal MTR 2756 G allele was associated with uteroplacental insufficiency (P =.022, likelihood ratio = 10.4) and maternal homocysteine (P =.017). The maternal MTR A2756G polymorphism was associated with uteroplacental insufficiency (P =.049, likelihood ratio = 6.0), but only in mothers not supplementing with high-dose B-vitamins. The maternal MTHFD1 AA genotype was associated with intrauterine growth restriction (P =.047, likelihood ratio = 5.8). CONCLUSION: This study suggests the maternal and fetal MTR 2756 G allele is an important risk factor in the development of uteroplacental insufficiency. In addition, the maternal MTHFD1 1958 AA genotype may be associated with intrauterine growth restriction.