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 methylenetetrahydrofolate reductase (MTHFR) deficiency due to the synthesis of a thermolabile variant of the enzyme with impaired catalytic activity which leads to reduced 5-methyltetrahydrofolate (5-methyl-THF) and mildly elevated homocysteine plasma concentrations when folate status is inadequate. To investigate whether the number of offspring is influenced by this mutation, we determined 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). Mothers with the 677C-->T mutation had a 2.28 times lower risk of having a twin pregnancy than those without (95% confidence interval = 1.18-4.66; P = 0.008). Our observation would explain, at least in part, the hereditary trait of multiple gestations and is in agreement with the ethnic distribution pattern of the T allele which has been found to be inversely correlated with the incidence of dichorionic twins. Our findings suggest that the MTHFR 677C-->T mutation interferes with human brood size, probably by influencing the proliferation of rapidly dividing embryonic and maternal cells.
Hasbargen
U
U
Department of Obstetrics and Gynecology, Klinikum der Universität München, Grosshadern, Munich, Germany. hasbargen@gyn.med.uni-muenchen.de
Lohse
P
P
Thaler
C J
CJ
D000022:Abortion, Spontaneous / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000483:Alleles; D002823:Chorion; D005260:Female; D005865:Gestational Age; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008423:Maternal Age; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D009154:Mutation; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000172:deficiency / Q000235:genetics*; D010298:Parity; D011247:Pregnancy; D011272:Pregnancy, Multiple / Q000235:genetics*; D014429:Twins, Dizygotic
D000587:Oxidoreductases Acting on CH-NH Group Donors; D042965:Methylenetetrahydrofolate Reductase (NADPH2)