The number of dichorionic twin pregnancies is reduced by the common MTHFR 677C -> T mutation

In multiple pregnancies, demands for folic acid are considerably increased. The most common inborn error of folate metabolism is mild methylenetetrahy drofolate reductase (MTHFR) deficiency due to the synthesis of a thermolabi le variant of the enzyme with impaired catalytic activity which leads to re duced 5-methyltetrahydrofolate (5-methyl-THF) and mildly elevated homocyste ine plasma concentrations when folate status is inadequate. To investigate whether the number of offspring is influenced by this mutation, we determin ed the frequency of the 677C-->T substitution in 156 singleton and 40 twin mothers with dichorionic placentation, The T allele frequency in singleton (0.30) and twin mothers (0.16) was significantly different (P = 0.011). Mot hers with the 677C-->T mutation had a 2.28 times lower risk of having a twi n pregnancy than those without (95% confidence interval = 1.18-4.66; P = 0, 008), Our observation mould explain, at least in part, the hereditary trait of multiple gestations and is in agreement with the ethnic distribution pa ttern of the T allele which has been found to be inversely correlated with the incidence of dichorionic twins. Our findings suggest that the MTHFR 677 C-->T mutation interferes with human brood size, probably by influencing th e proliferation of rapidly dividing embryonic and maternal cells.