XRCC1 is involved in repair of single-strand breaks generated by mutagenic exposure. Polymorphisms within XRCC1 affect its ability to efficiently repair DNA damage. Polycyclic aromatic hydrocarbons or PAHs are genotoxic compounds which form bulky DNA adducts that are linked with infertility. Few reports suggest combined role of XRCC1 polymorphisms and PAHs in infertility. Present study investigates association of three XRCC1 polymorphisms (p.Arg194Trp, p.Arg280His, p.Arg399Gln) with male and female infertility in a North-West Indian population using case–control approach. Additionally, in silico approach has been used to predict whether XRCC1 polymorphisms effect interaction of XRCC1 with different PAHs. For case–control study, XRCC1 polymorphisms were screened in peripheral blood samples of age- and gender-matched 201 infertile cases (♂-100, ♀-101) and 201 fertile controls (♂-100, ♀-101) using PCR–RFLP method. For in silico study, AutoDock v4.2.6 was used for molecular docking of B[a]P, BPDE-I, ( ±)-anti-BPDE, DB[a,l]P, 1-N, 2-N, 1-OHP, 2-OHF with XRCC1 and assess effect of XRCC1 polymorphisms on their interaction. In case–control study, statistical analysis showed association of XRCC1 p.Arg280His GA genotype (p = 0.027), A allele (p = 0.019) with reduced risk of male infertility. XRCC1 p.Arg399Gln AA genotype (p = 0.021), A allele (p = 0.014) were associated with reduced risk for female primary infertility. XRCC1 p.Arg194Trp T allele was associated with increased risk for female infertility (p = 0.035). In silico analysis showed XRCC1–PAH interaction with non-significant effect of XRCC1 polymorphisms on predicted binding. Therefore, present study concludes that XRCC1 polymorphism-modified risk for male and female infertility in North-West Indians without significant effect on predicted XRCC1–PAH interactions. This is the first report on XRCC1 in female infertility.

XRCC1 参与修复因诱变暴露而产生的单链断裂。XRCC1内的多态性影响其有效修复 DNA 损伤的能力。多环芳烃或 PAH 是一种基因毒性化合物，可形成大量 DNA 加合物，与不孕不育有关。很少有报告表明XRCC1多态性和 PAH 在不孕症中的共同作用。本研究采用病例对照方法调查了印度西北部人群中三种XRCC1多态性（p.Arg194Trp、p.Arg280His、p.Arg399Gln）与男性和女性不育症的关联。此外，计算机方法已用于预测XRCC1多态性是否影响 XRCC1 与不同 PAH 的相互作用。对于病例对照研究，使用 PCR-RFLP 在年龄和性别匹配的 201 名不孕病例 (♂-100, ♀-101) 和 201 名可育对照 (♂-100, ♀-101) 的外周血样本中筛查 XRCC1多态性方法。对于计算机模拟研究，使用 AutoDock v4.2.6 对 B[a]P、BPDE-I、(±)-anti-BPDE、DB[a,l]P、1-N、2-N、1 进行分子对接-OHP、2-OHF 与 XRCC1 并评估XRCC1多态性对其相互作用的影响。在病例对照研究中，统计分析显示XRCC1 p.Arg280His GA 基因型 ( p  = 0.027)、A 等位基因 ( p  = 0.019) 与男性不育风险降低相关。XRCC1 p.Arg399Gln AA 基因型 ( p  = 0.021)、A 等位基因 ( p  = 0.014) 与女性原发性不孕风险降低相关。XRCC1 p.Arg194Trp T 等位基因与女性不孕风险增加相关 ( p  = 0.035)。计算机分析显示 XRCC1-PAH 相互作用， XRCC1多态性对预测的结合没有显着影响。因此，本研究得出结论，XRCC1多态性改变了西北印度人男性和女性不育的风险，但对预测的 XRCC1-PAH 相互作用没有显着影响。这是关于XRCC1在女性不孕症中的第一份报告。