Reply:

In reply to Armando Reyes-Engel's comment 'Human genetic selection by folates', we make clear reference in our Nature Reviews Genetics article1 to the fact that the finding, which shows the use of periconceptional folate to prevent neutral-tube defects has led to an increase in the prevalence of 677TT MTHFR, is attributed to Muñoz-Moran and colleagues2. The reference to our former paper3 was merely intended to focus the reader to a broad overview of this area — this fact not withstanding, this previous paper3 also clearly documents the achievements of Muñoz-Moran and colleagues2, along with others who have carried out seminal work in this area, and who have provided a basis for believing that genetic selection might be occurring. Clearly, as the title of their Lancet paper (which we cite) implies, Reyes-Engel's research group had looked at genetic selection and folate intake back in 1998 (Ref. 2). We recognize the importance of this, and other crucial work by these authors4, and apologize for any perceived failing on our part to present a balanced review of the literature. However, clearly we did not author the associated News article. It should be remembered that the raison d'etre of this article was about the probable effect of mandatory supplementation of grain with folate. This population measure has now been implemented in many countries and warrants continuing attention. I believe that our expertise gained over many years in studying folate-nutritional biochemistry, including any effects that are imposed by B-vitamin gene variants, makes us particularly suitable candidates to comment on this issue. Readers that are interested in further study on genetic selection, which is based on this concept, should read the 2002 paper by Reyes-Engel and colleagues.4