DNA repair gene XRCC1 and XPD polymorphisms and the risk of idiopathic azoospermia in a Chinese population

Abstract

Abstract. Genetic polymorphisms in DNA repair genes may influence individual variation in DNA repair capacity and further influence the risk of developing cancer. However, little information is available on these polymorphisms in infertility. To investigate whether polymorphisms in DNA repair genes, X-ray repair cross-complementing group 1 (XRCC1) and xeroderma pigmentosum group D (XPD), alone or in combination, are associated with the risk of developing idiopathic azoospermia, the genotype and allele frequencies of three observed polymorphisms (XRCC1 Arg194Trp and Arg399Gln, and XPD Lys751Gln) were examined by polymerase chain reaction-restriction fragment length polymorphism based on a Chinese population consisting of 171 idiopathic azoospermia patients and 247 normal-spermatogenesis fertile controls. Associations between the polymorphisms and the idiopathic azoospermia risk were estimated by logistic regression, and the Statistical analysis system was used to test the gene-gene joint effects. All observed polymorphisms were in agreement with Hardy-Weinberg equilibrium. The XPD 751Gln allele seemed to be a risk allele for azoospermia, with a frequency of 11.40% in the cases and 5.67% in the controls (p=0.004). Compared with the Lys/Lys genotype, the XPD 751 Lys/ Gln+Gln/Gln genotype was associated with a moderately increased risk of azoospermia (OR=2.09), while the risk increased 5.100-or 3.064-fold, respectively, when combined with the XRCC1 194 Arg/Arg or 399 Arg/Arg genotype. In conclusion, our study provided the first evidence that the XPD and XRCC1 polymorphisms contributed to the risk of developing idiopathic azoospermia in a selected Chinese population. IntroductionEndogenous and exogenous mutagens may cause DNA damage in most cells including somatic and germ cells, and as a result, patients may manifest azoospermia (1). It has been clarified that DNA damage was more frequent in patients with complete spermatogenesis failure as compared to patients with incomplete spermatogenesis failure (2). However, humans have developed a set of complex DNA repair systems to safeguard the integrity of the genome by defending harmful consequences of DNA damage. Among the DNA repair systems, the base excision repair (BER) and nucleotide excision repair (NER) pathways are two crucial mechanisms that correct the localized small lesions and bulky DNA damage, respectively (3).Up to now, more than 150 human DNA repair genes in several distinct pathways have been identified, and most are known to have genetic variation in humans (4,5). In the present study, we focus on two well-studied DNA repair genes, X-ray repair cross-complementing group 1 (XRCC1) and xeroderma pigmentosum group D (XPD).XRCC1 encodes a protein involved in DNA BER that is essential in drawing different components of BER to the site of DNA damage and promoting efficiency of the BER pathway (6,7). The XRCC1 gene expresses conservatively and significantly high in the testis (8,9), especially in pachytene spermatocytes and round spermatids, maintaining the sp...