Nucleotide-excision repair system is critical for the removal of bulky DNA adducts during spermatogenesis,and its dysfunction might be related to male infertility.To explore the biomarker of genetic susceptibility for male infertility,we investigated the associations between the variants in NER genes and sperm DNA damage as well as the semen quality.Genotypes were determined by PCR-RFLP,and sperm DNA damage was evaluated by TUNEL assay.Based on a case-only study consisting of 620 infertile men,we found a significant association of XPA(-4) polymorphism with sperm DNA fragmentation.Individuals carrying the XPA (-4) A allele showed higher sperm DNA fragmentation and lower sperm concentration compared with the G allele carriers.Furthermore,we explored the contribution of this polymorphism to the risk of male infertility in a case-control study including 620 patients and 385 controls,which revealed a 1.52-fold (95% CI,1.08-2.02) risk for developing male infertility of the XPA (-4) AA carriers compared with noncarriers.By luciferase assay we verified that the XPA(-4) A allele had a lower transcriptional activity than the XPA (-4) G allele.In conclusion,these data provided first evidence that genetic polymorphisms in XPA promoter altered its transcriptional activity and,thus,might be a marker for genetic susceptibility to sperm DNA damage and male infertility in Chinese populations.