title: Human genetic selection on the MTHFR 677C>T polymorphism.
abstract: BACKGROUND
  The prevalence of genotypes of the 677C>T polymorphism for the MTHFR gene varies among humans. In previous studies, we found changes in the genotypic frequencies of this polymorphism in populations of different ages, suggesting that this could be caused by an increase in the intake of folate and multivitamins by women during the periconceptional period. The aim was to analyze changes in the allelic frequencies of this polymorphism in a Spanish population, including samples from spontaneous abortions (SA).
  
  
  METHODS
  A total of 1305 subjects born in the 20th century were genotyped for the 677C>T polymorphism using allele specific real-time PCR with Taqman probes. A section of our population (n = 276) born in 1980-1989 was compared with fetal samples (n = 344) from SA of unknown etiology from the same period.
  
  
  RESULTS
  An increase in the frequency of the T allele (0.38 vs 0.47; p < 0.001) and of the TT genotype (0.14 vs 0.24; p < 0.001) in subjects born in the last quarter of the century was observed. In the 1980-1989 period, the results show that the frequency of the wild type genotype (CC) is about tenfold lower in the SA samples than in the controls (0.03 vs 0.33; p < 0.001) and that the frequency of the TT genotype increases in the controls (0.19 to 0.27) and in the SA samples (0.20 to 0.33 (p < 0.01)); r = 0.98.
  
  
  CONCLUSIONS
  Selection in favor of the T allele has been detected. This selection could be due to the increased fetal viability in early stages of embryonic development, as is deduced by the increase of mutants in both living and SA populations.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Malaga, Malaga 29071, Spain. dralvaromayor@gmail.com
authors.forename: Alvaro
authors.initials: A
authors.lastname: Mayor-Olea
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Callejón
authors.forename: Arturo R
authors.initials: AR
authors.lastname: Palomares
authors.forename: Ana J
authors.initials: AJ
authors.lastname: Jiménez
authors.forename: María Jesús
authors.initials: MJ
authors.lastname: Gaitán
authors.forename: Alfonso
authors.initials: A
authors.lastname: Rodríguez
authors.forename: Maximiliano
authors.initials: M
authors.lastname: Ruiz
authors.forename: Armando
authors.initials: A
authors.lastname: Reyes-Engel
mesh_terms: D037881:Aborted Fetus / Q000201:enzymology*; D000328:Adult; D000367:Age Factors; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012641:Selection, Genetic; D013030:Spain; D055815:Young Adult
chemical_list: D042965:Methylenetetrahydrofolate Reductase (NADPH2)