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

Abstract

Purpose We investigated if substitutions in the ERCC1, ERCC2, and XRCC1 genes of the DNA repair pathway correlate with non-obstructive azoospermia and male infertility. Methods A total of 548 azoospermic infertile males and 410 fertile controls were genotyped for XRCC1 399A > G, 280G > A, and ERCC1 C > A 3′ UTR and 541 azoospermic infertile males and 416 fertile controls were genotyped for ERCC2 751A > C using iPLEX Gold Assay. Meta-analyses were performed on XRCC1 399A > G (1022 cases and 1004 controls), ERCC1 C > A 3′ UTR (879 cases and 1059 controls), and ERCC2 751A > C (914 cases and 850 controls) polymorphisms to quantitatively estimate the significance of the association between these polymorphisms and the risk of infertility. Results Statistically significant association between ERCC2 751A > C SNP and male infertility was found using the codominant model (p = 0.03). Results of meta-analysis suggested a lack of correlation with male infertility risk, which could be due to pooling of studies from different ethnic populations. Due to limited the number of studies, a stratified analysis for different ethnic groups could not be performed. Conclusion (s) In conclusion, AA genotype of 751A > C SNP in ERCC2 correlated with a higher risk of male infertility and may contribute to an increased risk of azoospermia and male infertility in Indian men.

Telomere Length and Male Fertility

“…Finally, Sato and colleagues in a GWAS conducted in the Japanese population reported an additional risk variant [ 18 ]. In addition to GWAS, several gene candidate studies have been conducted analyzing infertility parameters as outcomes [ 19 , 20 , 21 , 22 , 23 , 24 ]. Considering that male infertility is a common condition and almost half of the cases are idiopathic, the discovery of novel genetic variants is of the utmost importance to further our knowledge on this field of research.…”

Association between X‐ray repair cross‐complementing group 1 Arg399Gln polymorphism and male infertility: An update meta‐analysis

“…Then, one article (Gu et al., 2007) was excluded because of overlapping data through full‐text screening. Finally, six case–control articles with 1,886 patients and 1,212 controls were included in our meta‐analysis (Akbas et al., 2019; Garcia‐Rodriguez, et al., 2018; Ghasemi et al., 2017; Ji et al., 2010; Singh, Bansal, et al, 2019; Zheng et al., 2012). The detailed selection process was shown in Figure 1.…”

“…Compared with two previous relative meta‐analyses (Ibrahimi et al., 2019; Singh, Bansal, et al, 2019), we added two new original articles (Akbas et al., 2019; Garcia‐Rodriguez, et al., 2018). In addition, we changed or deleted some papers which were included in previous studies.…”

“…The main controversy consisted in two papers (Gu et al., 2007; Ji et al., 2010). Ibrahimi et al (Ibrahimi et al., 2019) included both of the two papers; however, Singh, Bansal, et al (2019) excluded Ji's paper (Ji et al., 2010) because they thought that Ji's article aimed to study the joint effects of ERCC2 polymorphisms and polycyclic aromatic hydrocarbon exposure on male infertility. In our study, after reading the full text of Ji's research, we found that all the cases were recruited from regular patients and fertility males without any intervention such as whether cases were exposed in environmental pollution, indicating that Ji's paper fulfilled our inclusion criteria.…”

“…However, others found little statistic association between XRCC1 Arg399Gln and male infertility risk (Akbas, Balkan, Binici, & Gedik, 2019; Ji et al., 2010). Although two well‐designed meta‐analyses on this topic had been conducted in 2019 (Ibrahimi et al., 2019; Singh, Bansal, et al, 2019), more related articles were published thereafter. The conclusion remains inconsistent and controversial.…”