Sirs

The aim of a recent paper by Lucock and Yates1 is to show the possible genetic selection that takes place as a result of folate intake by women during the periconceptional period.

I was pleasantly surprised by the fact that a topic already proposed by our team in 1998 (Ref. 2) has been revived. But I remained perplexed when I read the Opinion article, and the subsequent News article in news@nature.com, and saw that the proposal of genetic selection is attributed to Lucock and colleagues. Not only did we propose the possibility of such selection 7 years ago in the Lancet2, we subsequently quantified it3. To speculate or to hypothesize on genetic selection, the main observation needs to be the detection of phenotypic or genotypic changes in a population, through time or across generations. After an extensive review of the literature, we have not found any publication that studies the evolution of the C677T polymorphism in successive human generations to detect genetic selection, except our papers that were published in 1998 and 2002 (Refs 2,3).

Lucock and Yates say that, “recent findings indicate that exposure to elevated levels of this vitamin during the periconceptional period could select embryos that carry the mutant 677T MTHFR allele22.” This reference does not correspond to the sentence. Reference 22 in their paper is an article published by Lucock et al. in Nutrition Research4. The authors summarize the article in the abstract paragraph, “We look at three particular phenomena that link folate status/genes to evolutionary pressures: 1) The evolution of pigmentation to avert the impact of UV light on labile folates needed for development processes. [An hypothesis that was published years ago2.] 2) The effect of C677T-MTHFR on foetal survival prevalence. [The term prevalence was used by Lucock et al. with a population of controls (n = 32) and mothers with NTD pregnancy (n = 20).] 3) The ability of folate to mask harmful developmental mutations.” They do not study possible genetic selection in this article. They just propose factors that could exert some influence on developmental processes. As a matter of fact, they have not published any articles that study genetic selection on the basis of this concept.

In another paragraph in their Nature Reviews Genetics article they say, “In an earlier study, the use of periconceptional folic-acid supplements as a preventive agent for neural-tube defects had already been shown to increase the prevalence of individuals with the MTHFR 677TT genotype26” and this reference is to our Lancet article from 1998. But they do not mention that in this article we proposed the possibility of genetic selection in human beings. Despite the fact that the term 'genetic selection' was in the title of the article2.

The Opinion article by Lucock and Yates is disappointing, mainly because it fails to acknowledge the work3 that gathered enough population data to demonstrate a possible genetic selection, following our initial controversial publication2.