Sirs

We read the recent Review by Lucock and Yates with interest1. The authors postulate that improved folate nutrition either through periconceptional supplementation with folic acid or through mandatory fortification of foodstuffs is exerting a strong selective pressure on the MTHFR 677C>T polymorphic variant.

Analysis of this locus in a UK population of mothers (n = 512) and neonates (n = 578) indicates that the frequency of the 677TT genotype is not increased in neonates (TT = 11.1% (95% CI 8.6–13.9)) when compared with mothers (TT = 13.1% (95% CI 10.3–16.3)) (Ref. 2).

Red blood cell folate was measured using immunoassay methodology, in a subset of these women during early pregnancy (n = 282). To further test the hypothesis of Lucock and Yates, we examined the distribution of neonatal genotypes in relation to log-transformed maternal folate status. We found no difference in distribution of neonatal genotype by maternal folate status.

Previously, analysis showed no evidence that mean red cell folate levels in pregnant women with the MTHFR TT genotype differed significantly from those with the MTHFR CC genotype, indicating that the MTHFR genotype does not directly influence the amount of stored folate3. However, when those women in the highest quintile of red cell folate status were considered, a marked increase in the frequency of the 677TT genotype was observed (OR 4.73 (95% CI 1.92–11.59) p = 0.001). If this observation is real, this indicates that high folate status might overcome the potentially detrimental influence of the TT genotype in allowing a viable pregnancy and birth to occur4,5.

Although there was no discernible difference in the distribution of MTHFR 677C>T genotypes in the offspring of these women, ultimately the 677T allele frequency might be expected to increase slowly over the course of a number of generations if women with this genotype are more likely to have successful pregnancies as population folic acid intake increases. This in turn would create a 'folic acid habit' as alluded to by the authors.