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-methylenetetrah ydrofolate reductase gene is a risk factor for placental vasculopathy (abru ptio placentae or placental infarction with fetal growth restriction). STUDY DESIGN: This case-control study enrolled 165 women with placental vas culopathy and 139 matched control women with normal pregnancy outcomes. Mea surements included fasting total plasma homocysteine concentration, serum a nd red blood cell folate concentrations, serum vitamin B-12 concentration, whole-blood vitamin Se concentration, and analysis of the 5,10-methylenetet rahydrofolate reductase gene C677T mutation. RESULTS: The median total plasma homocysteine concentration was significant ly 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 ge notype for the mutated 5,10-methylenetetrahydrofolate reductase gene was fo und 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 place ntal vasculopathy, for which homozygosity for a mutated 5,10-methylenetetra hydrofolate reductase gene was found to be a new risk factor. The risk of p lacental vasculopathy probably increases in conditions of low serum folate concentration.