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

• Published in: Journal of assisted reproduction and genetics 2019-01, Vol.36 (1), p.79-90
• Main Authors: Singh, Vertika, Bansal, Sandeep Kumar, Sudhakar, D. V. S., Neelabh, Chakraborty, Arijit, Trivedi, Sameer, Gupta, Gopal, Thangaraj, Kumarasamy, Rajender, Singh, Singh, Kiran
• Format: Article
• Language: English
• Subjects: 3' Untranslated regions; Asia - epidemiology; Asians - genetics; Case-Control Studies; DNA Repair; DNA-Binding Proteins - genetics; Endonucleases - genetics; ERCC1 protein; Genetics; Gynecology; Human Genetics; Humans; Infertility; Infertility, Male - epidemiology; Infertility, Male - genetics; Infertility, Male - pathology; Male; Males; Medicine; Medicine & Public Health; Meta-analysis; Minority & ethnic groups; Polymorphism, Single Nucleotide; Population studies; Reproductive Medicine; Single-nucleotide polymorphism; Statistical analysis; X-ray Repair Cross Complementing Protein 1 - genetics; Xeroderma Pigmentosum Group D Protein - genetics; XRCC1 protein
• ISSN: 1058-0468; 1573-7330
• DOI: 10.1007/s10815-018-1339-6

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.