title: DNA repair genes XPD and XRCC1 polymorphisms and risk of end-stage renal disease in Egyptian population.
abstract: DNA repair gene polymorphisms may affect DNA repair capacity and modulate susceptibility to end-stage renal disease (ESRD). We aimed to determine the association of polymorphisms in xeroderma pigmentosum complementation group D (XPD) and X-ray cross-complementing group 1 (XRCC1) with ESRD development. Polymorphisms in XPD codons 312 and 751 and XRCC1 codon 399 were genotyped in 98 patients undergoing hemodialysis and 102 healthy controls using polymerase chain reaction and restriction fragment length polymorphism. Patients having XRCC1-399 Arg/Gln genotype or XRCC1-399 Gln/Gln genotype had a significantly higher risk of ESRD than those with XRCC1-399 Arg/Arg [odds ratio (OR): 2.48; 95% confidence intervals (CI): 1.36-4.52; p = 0.004 and OR: 4.05; 95% CI: 1.19-13.73; p = 0.03, respectively]. We also found a significantly higher frequency of the XRCC1 399Gln allele in patients with ESRD than in controls (OR: 2.22; 95% CI: 1.16-4.25; p = 0.02). Combination of the Arg/Gln or Gln/Gln genotypes of XRCC1 Arg399Gln polymorphism with Asp/Asn or Asn/Asn genotypes of XPDAsp312Asn or with the Lys/Gln or Gln/Gln genotypes of XPD Lys751Gln was significantly associated with the development of ESRD. Haplotypes association showed that association of Gln allele of XRCC1 Arg399Gln polymorphism with the Asn allele of XPDAsp312Asn polymorphism (p = 0.004) or Gln allele of XRCC1 Arg399Gln polymorphism with the Gln allele of XPD Lys751Gln polymorphism (p = 0.003) was highly significantly associated with the development of ESRD. This study revealed that XRCC1 Arg399Gln polymorphism may confer increased risk for the development of ESRD. Furthermore, larger studies should be conducted to confirm these results.
authors.affiliation: Department of Clinical Pathology, Faculty of Medicine, Menoufia University , Menoufia , Egypt .
authors.forename: Wafaa M
authors.initials: WM
authors.lastname: Radwan
authors.forename: Hany S
authors.initials: HS
authors.lastname: Elbarbary
authors.forename: Nevein M
authors.initials: NM
authors.lastname: Alsheikh
mesh_terms: D000328:Adult; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics*; D004151:Dipeptides / Q000235:genetics; D004534:Egypt; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007676:Kidney Failure, Chronic / Q000235:genetics / Q000628:therapy; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D006435:Renal Dialysis / Q000379:methods; D000076105:X-ray Repair Cross Complementing Protein 1; D014983:Xeroderma Pigmentosum / Q000150:complications / Q000235:genetics; D051759:Xeroderma Pigmentosum Group D Protein / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; D004151:Dipeptides; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human; C578860:arginyl-glutamine; C076685:arginylarginine; D051759:Xeroderma Pigmentosum Group D Protein
keywords: Dialysis; XPD; XRCC1; end-stage renal disease; polymorphism