Role of XRCC1, XPC, NBN gene polymorphisms in spermatogenesis

Abstract

The damaging effect of chemical, physical and biological factors on germ cells has an important role in the pathogenesis of male infertility. Maintaining integrity and stability of the genetic information of male germ cells is carried out by the DNA repair system. Data on the association of DNA repair system gene polymorphisms with pathospermia are few and contradictory. The study of the DNA repair system gene polymorphisms among men with various types of pathospermia can provide essential information for the formation of groups with an increased risk of disturbances in the process of spermatogenesis. The aim of this work is investigating the role of polymorphisms of genes of the DNA repair system as factors of predisposition to male infertility, as well as to study their intergenic interaction. In this study the frequency of repair system gene polymorphisms (XRCC1 rs25487, rs25489; NBN rs1805794 and XPC rs2228001) was tested in reproductive-age men of the population of Rostov region. The samples were classified into four groups according to semen analyses: normozoospermia, oligozoospermia, asthenozoospermia and the combined group with pathospermia. As a result, we found that the Arg280His (839G>A) (rs25489) polymorphism of the XRCC1 gene may be associated with an impairment of the human spermatogenesis process. In men with genotype Arg/His comparing with genotype Arg/Arg it was more often found reducing the spermatozoa concentration (OR 4.26; 95% CI 1.02–17.75; p < 0.05). Variant His/His also may be associated with an increased risk of oligozoospermia (OR 4.77; 95% CI 0.19–120.47; p < 0.05). The data obtained in this work are a step towards proving that polymorphic variants of the DNA repair system genes XRCC1, XPC and NBN contribute to the risk of pathospermia.