DNA repair XRCC1 Arg399Gln polymorphism is associated with the risk of development of end-stage renal disease

Abstract

Patients with end-stage renal disease (ESRD) display enhanced genomic damage. DNA repair gene polymorphisms may affect DNA repair capacity and modulate susceptibility to ESRD. In this study, we aimed to determine the frequency of polymorphisms in two DNA repair enzyme genes, Xeroderma pigmentosum complementation group D (XPD) and X-ray cross-complementing group 1 (XRCC1), in patients with ESRD and to evaluate their association with ESRD development. By using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP), we genotyped four single nucleotide polymorphisms (SNPs) in XPD codons 312 and 751 and XRCC1 codons 194 and 399 in 136 dialysis patients (71 patients undergoing hemodialysis and 65 subjected to peritoneal dialysis) and 147 healthy controls. Patients having XRCC1 399 Arg/Gln (OR:1.98; 95% CI: 1.21-3.25, P = 0.007) or XRCC1-399 Gln/Gln (OR: 3.95; 95% CI: 1.45-10.76, P = 0.005) genotype had a significantly higher risk of ESRD than those with XRCC1 399 Arg/Arg genotype. We also found a significantly higher frequency of the XRCC1 399Gln allele in patients with ESRD than in controls, with OR = 2.03 (95% CI = 1.08-3.81, P = 0.03). We further investigated the potential combined effect of these DNA repair variants on the risk of ESRD development. It was found that combination of the Arg/Gln or Gln/Gln genotypes of XRCC1 Arg399Gln polymorphism with the two possible genotypes of XPD-Asp312Asn or with the Lys/Gln or Gln/Gln genotypes of XPD Lys751Gln was significantly associated with the development of ESRD. This is the first report showing an association between DNA repair gene polymorphisms and ESRD development, and suggests that XRCC1 Arg399Gln polymorphism may confer increased risk for the development of the disease. Further larger studies should be conducted to confirm these results.

DNA repair genes XPD and XRCC1 polymorphisms and risk of end-stage renal disease in Egyptian population

“…We also found no significant association between the XPD 312Asn and 751Gln alleles and ESRD risk. Our findings are in agreement with the results reported by Trabulus et al 35 in Turkish population. The frequencies of XPD 312Asn and 751Gln alleles in our ESRD patients were 0.35 and 0.37, whereas in controls they were 0.36 and 0.37, respectively.…”

“…These results suggest that the XRCC1 Arg399Gln polymorphism may contribute to ESRD development. Our findings are in agreement with the study conducted by Trabulus et al 35 who reported similar finding in Turkish population. It is also consistent with the published functional studies that reported some association between XRCC1 Arg399Gln polymorphism and markers of DNA damage.…”

“…These results are in agreement with Trabulus et al study. 35 We did not find any association between combination of Asp/Asp genotype of XPDAsp312Asn polymorphism with Arg/Gln or Gln/Gln genotypes of XRCC1 Arg399Gln polymorphism and ESRD risk. This is in contrast to the Trabulus et al 35 findings, who reported a positive association between these combined genotypes and ESRD in Turkish population.…”

“…The frequencies of XPD 312Asn and 751Gln alleles in our ESRD patients were 0.35 and 0.37, whereas in controls they were 0.36 and 0.37, respectively. Trabulus et al 35 analyzed the XPDAsp312Asn and Lys751Gln polymorphism on a cohort which included 136 dialysis patients and 147 controls from Turkey. The frequency of the variant XPD 312Asn and 751Gln alleles were 0.46 and 0.43 in cases and 0.40 and 0.43 in controls.…”

Association of Endothelial Nitric Oxide Synthase Glu298Asp Gene Polymorphism with the Risk of End-Stage Renal Disease

“…5,6 Patient suffering from ESRD displays enhanced genomic damage, and DNA repair gene polymorphisms may affect DNA repair capacity and modulate susceptibility to ESRD. 7 Some current investigations [8][9][10] suggested that genetic factors might play a key role in the onset of ESRD.…”