title: Genetic selection? A study of individual variation in the enzymes of folate metabolism.
abstract: BACKGROUND
  Genetic variation in folate metabolism has been associated with survival in utero, the success of in vitro fertilisation, multiple pathologies and longevity.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: School of Medicine, Health Policy and Practice, University of East Anglia, Norwich NR4 7TJ, UK. b.jennings@uea.ac.uk
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Jennings
authors.forename: Gavin A
authors.initials: GA
authors.lastname: Willis
authors.forename: Jane
authors.initials: J
authors.lastname: Skinner
authors.forename: Caroline L
authors.initials: CL
authors.lastname: Relton
mesh_terms: D020121:5' Untranslated Regions; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D015331:Cohort Studies; D005492:Folic Acid / Q000235:genetics / Q000378:metabolism*; D005787:Gene Frequency; D014644:Genetic Variation; D005838:Genotype; D006720:Homozygote; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D013940:Thymidylate Synthase / Q000235:genetics*
chemical_list: D020121:5' Untranslated Regions; D005492:Folic Acid; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D013940:Thymidylate Synthase