Variation of the genes encoding antioxidant enzymes SOD2 (rs4880), GPX1 (rs1050450), and CAT (rs1001179) and susceptibility to male infertility: a genetic association study and in silico analysis.

Abstract

Enzymatic factors including superoxide dismutase (SOD), glutathione peroxidase (GPX), and catalase (CAT) are among the most important protective antioxidant systems in human semen. This study was conducted to investigate the association between the activities of the mentioned enzymes in semen and also the association between SOD2 rs4880, GPX1 rs1050450, and CAT rs1001179 polymorphisms with male infertility, which was followed by a bioinformatics approach. In a case-control study, 223 infertile men and 154 healthy fertile men were included in the study. After extracting genomic DNA from semen samples, the genotype of rs1001179, rs1050450, and rs4880 polymorphisms was determined using the PCR-RFLP. Next, the activities of SOD, CAT, and GPX enzymes were also measured in semen. Bioinformatics software was used to investigate the effect of polymorphisms on the function of genes. Data analysis indicated that rs1001179 polymorphisms were not associated with male infertility. But our data revealed that the rs1050450 polymorphism is associated with a reduced risk of male infertility as well as asthenozoospermia and teratozoospermia. In addition, rs4880 polymorphism was associated with an increased risk of male infertility as well as teratozoospermia. Further analysis showed that the activity of the CAT enzyme in the infertile group is significantly higher than in the fertile group, but the activity of GPX and SOD enzymes in the infertile group is significantly lower than in the fertile group. Bioinformatic analysis showed that rs1001179 polymorphism affects the transcription factors binding site upstream of the gene, while rs1050450 and rs4880 polymorphisms had an essential role in protein structure and function. On the other hand, rs1050450 (T allele) was exposed to a reduced risk of male infertility and may be a protective factor. And SOD2 rs4880 (C allele) is associated with an increased risk of male infertility, and it is considered a risk factor for male infertility. To reach accurate results, we recommend that the study of SOD2 rs4880 and GPX1 rs1050450 polymorphism effects in the different populations with a larger sample size and meta-analysis are needed.