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Open Access Highly Accessed Research article

Genetic selection? A study of individual variation in the enzymes of folate metabolism

Barbara A Jennings1*, Gavin A Willis2, Jane Skinner1 and Caroline L Relton3

Author Affiliations

1 School of Medicine, Health Policy and Practice, University of East Anglia, Norwich NR4 7TJ, UK

2 Department of Molecular Genetics, Norfolk and Norwich University Hospital, Norwich NR4 7UY, UK

3 Institute for Ageing and Health and Human Nutrition Research Centre, Newcastle University, Royal Victoria Infirmary, Newcastle upon Tyne, NE1 4LP, UK

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BMC Medical Genetics 2010, 11:18  doi:10.1186/1471-2350-11-18

Published: 1 February 2010



Genetic variation in folate metabolism has been associated with survival in utero, the success of in vitro fertilisation, multiple pathologies and longevity.


We have looked at the prevalence of genetic variants of the enzymes MTHFR and TYMS in 2,898 DNA samples derived from five cohorts collected in the United Kingdom. The simultaneous analysis of genetic variants of the MTHFR and TYMS loci was carried out to investigate a putative gene-gene interaction that was first observed in an elderly male population from Norfolk.


We have made a consistent observation in five population cohorts; the proportion of individuals who are homozygous for the 2R allele of the 5'UTR TYMS polymorphism is less in individuals who are homozygous for the T allele of MTHFR 677 than in individuals homozygous for the C allele of MTHFR 677 (p = 0.02).


These data may suggest a gene-gene interaction and could be evidence of genetic selection, with some pregnancies more or less viable as a consequence of genetic variation. If these genetic phenomena affect the way folate is handled at the cellular level in utero it is possible that maternal folic acid intake may over-ride such genetic selection.