Polymorphisms of DNA repair genes XRCC1 and LIG4 and idiopathic male infertility

Abstract

Sperm DNA damage is one of the associated factors of idiopathic male infertility and abnormal spermatogenesis. This study was conducted to assess possible association between risk of male infertility with X-ray repair cross complementing group 1 (XRCC1) Arg399Gln (G to A) and DNA ligase 4 (LIG4) Thr9Ile (C to T) gene polymorphisms which are involved in different DNA repair pathways. In this case-control study 191 fertile and 191 infertile men (29-40 years old) were enrolled. The single-nucleotide polymorphism genotypes and alleles of XRCC1 Arg399Gln and LIG4 Thr9Ile were assessed using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. There was no significant association between XRCC1 Arg399Gln polymorphism and risk of male infertility. The frequency of LIG4 Thr9Ile genotypes and alleles were statistically different between fertile and infertile men (p<0.001). We found that the CT genotype increased infertility risk more than threefold (OR, 3.12; 95% CI, 1.803-5.407). The LIG4 TT genotype carriers had decreased progressive motile sperm (p<0.05) and increased non-progressive motile sperm (p<0.001) compared with the CC genotype. Moreover, sperm concentration in subjects carrying the CT genotype was lower than that observed in CC carriers (p<0.05). The results revealed that the GG/CT and GA/CT combinations of genotypes increase the risk of infertility 3.5 and fourfold, respectively (p=0.021 and 0.004, respectively). This study demonstrated that there was an association between LIG4 Thr9Ile polymorphism and male infertility and suggests CT genotype as a risk factor for male infertility.

The polymorphism of XRCC1 Arg399Gln (rs25487) and male infertility risk: a meta-analysis of 1,407 cases and 974 control studies

“…In this meta-analysis, 5 relevant studies were screened. While two of them demonstrate a signifi cant association between XRCC1 polymorphisms and male infertility (17,19) , the other selected studies do not show any notable association (18,20,21). Hence, this meta-analysis was performed to evaluate the association of XRCC1 and male infertility in a comprehensive manner.…”

SNPs in ERCC1, ERCC2, and XRCC1 genes of the DNA repair pathway and risk of male infertility in the Asian populations: association study, meta-analysis, and trial sequential analysis

“…For XRCC1 399A > G, our case-control study and the meta-analysis suggested a lack of correlation with male infertility risk. Out of the three previously published studies, two reported a lack of association [7,22]; however, the other study by Zheng et al reported that A can be Fig. 2 Forest plot showing the odds ratio, p value, and direction of association between ERCC2 751A > C, ERCC1 C > A 3′ UTR, and XRCC1 399A > G polymorphism and male infertility Fig.…”

“…The impact of polymorphism in the DNA repair pathway genes on male infertility risk has been studied in various populations [4,7,[21][22][23]. Most commonly studied SNPs belonged to the ERCC2, ERCC1, and XRCC1 genes.…”

“…The associations of rs13181, rs3212986, and rs25487 polymorphisms with male infertility risk have been previously evaluated across different populations [4,7,[21][22][23]. Hence, we performed meta-analyses on data pooled from all published studies to evaluate the association between these polymorphisms and male infertility.…”

“…ERCC2 751A > C, ERCC1 C > A, and XRCC1 399A > G polymorphisms have been previously studied in male infertility [4,7,[21][22][23]; however, the results so far have been inconsistent. Hence, we also performed meta-analyses on all eligible case-control studies to quantitatively estimate the significance of the association between these polymorphisms and the risk of male infertility.…”