PLoS ONE (Jan 2012)

Association of the MTHFR A1298C variant with unexplained severe male infertility.

  • Abdelmajid Eloualid,
  • Omar Abidi,
  • Majida Charif,
  • Brahim El Houate,
  • Houda Benrahma,
  • Noureddine Louanjli,
  • Elbakkay Chadli,
  • Maria Ajjemami,
  • Abdelhamid Barakat,
  • Anu Bashamboo,
  • Ken McElreavey,
  • Houria Rhaissi,
  • Hassan Rouba

DOI
https://doi.org/10.1371/journal.pone.0034111
Journal volume & issue
Vol. 7, no. 3
p. e34111

Abstract

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The methylenetetrahydrofolate reductase (MTHFR) gene is one of the main regulatory enzymes involved in folate metabolism, DNA synthesis and remethylation reactions. The influence of MTHFR variants on male infertility is not completely understood. The objective of this study was to analyze the distribution of the MTHFR C677T and A1298C variants using PCR-Restriction Fragment Length Polymorphism (RFLP) in a case group consisting of 344 men with unexplained reduced sperm counts compared to 617 ancestry-matched fertile or normozoospermic controls. The Chi square test was used to analyze the genotype distributions of MTHFR polymorphisms. Our data indicated a lack of association of the C677T variant with infertility. However, the homozygous (C/C) A1298C polymorphism of the MTHFR gene was present at a statistically high significance in severe oligozoospermia group compared with controls (OR = 3.372, 95% confidence interval CI = 1.27-8.238; p = 0.01431). The genotype distribution of the A1298C variants showed significant deviation from the expected Hardy-Weinberg equilibrium, suggesting that purifying selection may be acting on the 1298CC genotype. Further studies are necessary to determine the influence of the environment, especially the consumption of diet folate on sperm counts of men with different MTHFR variants.