Associations of variants in MTHFR and MTRR genes with male infertility in the Jordanian population

Gene. 2014 Feb 15;536(1):40-4. doi: 10.1016/j.gene.2013.12.001. Epub 2013 Dec 12.


Folate pathway is expected to play an important role in spermatogenesis since it is involved in DNA synthesis, repair and methylation. The purpose of this study was to examine the association between male infertility and the MTHFR (C677T and A1298C) and MTRR (A66G) polymorphisms. A group of 300 males was recruited in this study from different Jordanian infertility clinics. Of these, 150 cases of infertile men that included oligozoospermia cases (n=45), severe oligozoospermia (n=71) and azoospermia (n=34) were studied. The other 150 males were age matched fertile controls. Genotyping of MTHFR and MTRR polymorphisms was performed using PCR-RFLP technique. The results showed an association between MTHFR 677TT genotype and male infertility (P<0.05). However, the distribution of MTHFR A1298C and MTRR A66G genotypes were not different between the fertile and infertile groups (P>0.05). In addition, none of the examined polymorphisms was related to any of the semen parameters in the infertile group. In conclusion, this study showed that MTHFR C677T polymorphism is associated with male infertility in Jordanians.

Keywords: CI; DNA; EDTA; IVF; Infertility; Jordan; MTHFR; MTRR; Male; OR; PCR; RFLP; SNP; Single nucleotide polymorphism; confidence interval; deoxyribonucleic acid; ethylene diamine tetra-acetate; in vitro facilitated; methionine synthase reductase; methylene tetrahydrofolatereductase; odd ratio; polymerase chain reaction; restriction fragment length Polymorphism; single nucleotide polymorphism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Case-Control Studies
  • Ferredoxin-NADP Reductase / genetics*
  • Gene Frequency
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Infertility, Male / epidemiology
  • Infertility, Male / genetics*
  • Jordan / epidemiology
  • Male
  • Methylenetetrahydrofolate Reductase (NADPH2) / genetics*
  • Polymorphism, Restriction Fragment Length
  • Polymorphism, Single Nucleotide
  • Population / genetics


  • methionine synthase reductase
  • Ferredoxin-NADP Reductase
  • MTHFR protein, human
  • Methylenetetrahydrofolate Reductase (NADPH2)