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The DNA non-homologous end-joining repair gene XRCC6 (Ku70) plays an essential role in the DNA double-strand break (DSB) repairs. Defects in the DSB repair pathway results in genomic instability. Varicocele is characterized by high pressure and stasis in the veins of the testis. There is little knowledge about the molecular mechanisms underlying varicocele. One of the reasons for increased spermatozoa DNA damage is high concentrations of reactive oxygen species (ROS), which leads to DNA-DSBs. We assumed that a promoter T-991C (rs5751129) polymorphism in the XRCC6 gene was associated with susceptibility to varicocele in infertile men. Therefore, 63 infertile varicocele men and 150 healthy controls were recruited in our study. The healthy controls had no history of varicocele, and they were matched with patients by age. Our results showed that infertile varicocele patients and control groups had significant differences in the distribution of their genotypic and allelic frequency (p = 0.00) in the XRCC6 promoter T-991C polymorphism. Men who carried CC genotype had a 5.22-fold increased odds ratio of developing infertile varicocele compared to those who carried the wild-type TT genotype (95% CI 2.31–11.81, P < 0.001). Our results suggested that the CC genotype and the C allele in the promoter region of XRCC6 gene might play an important role in developing infertility in the varicocele men. Further research is needed to provide the effect of this polymorphism.

Association between genetic polymorphism of XRCC6 T-991C and risk of varicocele