A common mutation in the 5,10-methylenetetrahydrofolate reductase gene as a new risk factor for placental vasculopathy

OBJECTIVE: This study was undertaken to investigate whether the cytosine-to-thymine substitution at nucleotide 677 (C67TT) in the 5,10-methylenetetrahydrofolate reductase gene is a risk factor for placental vasculopathy (abruptio placentae or placental infarction with fetal growth restriction). STUDY DESIGN: This case-control study enrolled 165 women with placental vasculopathy and 139 matched control women with normal pregnancy outcomes. Measurements included fasting total plasma homocysteine concentration, serum and red blood cell folate concentrations, serum vitamin B-12 concentration, whole-blood vitamin Se concentration, and analysis of the 5,10-methylenetetrahydrofolate reductase gene C677T mutation. RESULTS: The median total plasma homocysteine concentration was significantly higher in the study group than in the control group (P<.01; odds ratio >97.5th percentile, 4.66; 95% confidence interval, 1.55-14.0). Homozygous genotype for the mutated 5,10-methylenetetrahydrofolate reductase gene was found in 12% of the study group and 5% of the control group (odds ratio, 2.45; 95% confidence interval, 1.00-6.02). CONCLUSIONS: Mild hyperhomocysteinemia was confirmed among women with placental vasculopathy, for which homozygosity for a mutated 5,10-methylenetetrahydrofolate reductase gene was found to be a new risk factor. The risk of placental vasculopathy probably increases in conditions of low serum folate concentration.