5,10-METHYLENETETRAHYDROFOLATE REDUCTASE GENETIC-POLYMORPHISM AS A RISK FACTOR FOR NEURAL-TUBE DEFECTS

Persons with a thermolabile form of the enzyme 5,10 methylenetetrahydr ofolate reductase (MTHFR) have reduced enzyme activity and increased p lasma homocysteine which can be lowered by supplemental folic acid. Th ermolability of the enzyme has recently been shown to be caused by a c ommon mutation (677C(-->)T) in the MTHFR gene. We studied 41 fibroblas t cultures from NTD-affected fetuses and compared their genotypes with those of 109 blood specimens from individuals in the general populati on. 677C(-->)T homozygosity was associated with a 7.2 fold increased r isk for NTDs (95% confidence interval: 1.8-30.3; p value: 0.001). Thes e preliminary data suggest that the 677C(-->)T polymorphism of the MTH FR gene is a risk factor for spina bifida and anencephaly that may pro vide a partial biologic explanation for why folic acid prevents these types of NTD.