Association of polymorphisms in genes coding for antioxidant enzymes and human male infertility

Although oxidative stress is thought to be an important cause of male infertility, primarily due to DNA and cell membrane damage, little is known about the genetic causes underlying suboptimal function of the seminal enzymatic antioxidant system. The aim of this study was to investigate the relationship of four potentially functional polymorphisms associated with oxidative stress pathway genes (superoxide dismutase-SOD2 lle58Thr and SOD2 rs4880, catalase-CAT C-262T, glutathione peroxidase 1-GPX1 Pro200Leu) and two null variants of the glutathione S transferase (GSTT and GSTM) genes and infertility risk.

A case control study was conducted on 313 infertile patients and 80 fertile donors. Each ejaculate was subjected to a seminal analysis that included the classical parameters seminal volume, sperm concentration, sperm motility, and sperm morphology, as well as sperm DNA fragmentation (patients only). Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and PCR multiplex methods were carried out for genotyping.

Statistically significant differences were found between fertile donors and infertile patients for SNP CAT C-262T; the CC genotype was related with a twofold increased risk of infertility (odds ratio [OR] = 2.262; 95% confidence interval [CI] = 1.369-3.733; P = 0.001), whereas the CT genotype was associated with a protective effect (OR = 0.401; 95% CI = 0.241-0.667; P = 0.001). Surprisingly, the SOD2 Ile58ssThr SNP was not represented in the sample population, so its frequency in the current population frequenting fertility clinics in Madrid may be very low.

Our results suggest that the CAT SNP C-262T is potentially associated with an increased risk of male infertility.