title: RRM1, RRM2 and ERCC2 Gene Polymorphisms in Coronary Artery Disease.
abstract: OBJECTIVE
  Coronary artery disease (CAD) is a chronic inflammatory disease seen as formation of atherosclerotic plaques (atheroma) in coronary arteries. Recent published papers show that DNA damage and repair mechanisms play a crucial role on the development and severity of atheromas. In this study, we investigated nucleotide excision repair (NER) pathway-related gene polymorphisms in atherosclerosis. XPD, encoded by ERCC2 gene, is an ATP-depended helicase enzyme involved in the NER pathway. Ribonucleotide reductase (RR) is a tetra meric enzyme, synthesizing deoxyribonucleotides from ribonucleotides for DNA synthesis. RR is encoded by the RRM1 and RRM2 genes, which are two subunits of RR enzyme.
  
  
  METHODS
  DNA samples isolated from peripheral blood were genotyped with real-time polymerase chain reaction (RT-PCR) for RRM1 (rs12806698), RRM2(rs6859180) and ERCC2 (rs13181) genes.
  
  
  RESULTS
  The frequency of the RRM1 AC heterozygote genotype was found to be significantly lower (odds ratio (OR)=0.369, 95% confidence interval (CI)=0.179-0.760; p=0.006), whereas the CC homozygote genotype was found to be significantly higher in patients compared to controls (OR=7.636, 95% CI=2.747-21.229; p=0.000). In addition, the RRM1 A allele was higher in control group (p=0.000, OR=0.131 95%CI=0.047-0.364). For the ERCC2 gene, GG genotype was significantly higher in control group (p=0.017, OR=0.387, 95%CI=0.175-0.152) and TT genotype (p=0.021) was higher in CAD group. TT genotype had a ~3-fold increased risk (OR=3.615, 95%CI=1.148-11.380) for CAD. Carrying T allele appears to be a risk factor for CAD (p=0.017, OR=2.586, 95%CI=1.173-5.699), while the G allele might be a risk-reducing factor (p=0.021, OR=0.277, 95%CI=0.088-0.871) for CAD.
  
  
  CONCLUSIONS
  RRM1 and ERCC gene polymorphisms, having homozygous mutant genotype, might be a risk factor for CAD. RRM1 and ERCC wild type alleles are risk-reducing factor for CAD. Also, carrying RRM1 A allele might have a protective effect for smokers.
authors: Department of Molecular Medicine, Institute of Health Sciences, Yeditepe University, Istanbul, Turkey.
authors: Emre Murat
authors: EM
authors: Altinkilic
authors: Department of Cardiovascular Surgery, Marmara University Pendik Education and Research Hospital, Istanbul, Turkey.
authors: Selim
authors: S
authors: Isbir
authors: Department of Biochemistry, Faculty of Medicine, Istanbul Bilim University, Istanbul, Turkey.
authors: Uzay
authors: U
authors: Gormus
authors: Department of Molecular Medicine, Institute of Health Sciences, Yeditepe University, Istanbul, Turkey.
authors: Seda Gulec
authors: SG
authors: Yilmaz
authors: Department of Biochemistry, Faculty of Medicine, Yeditepe University, Istanbul, Turkey.
authors: Altay Burak
authors: AB
authors: Dalan
authors: Department of Cardiovascular Surgery, Marmara University Pendik Education and Research Hospital, Istanbul, Turkey.
authors: Selvi
authors: S
authors: Duman
authors: Department of Medical Biology, Faculty of Medicine, Yeditepe University, Istanbul, Turkey turgay.isbir@yeditepe.edu.tr tisbir@superonline.com.
authors: Turgay
authors: T
authors: Isbir
mesh_terms: D000368:Aged; D000483:Alleles; D003324:Coronary Artery Disease / Q000235:genetics* / Q000473:pathology; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012262:Ribonucleoside Diphosphate Reductase / Q000235:genetics*; D012307:Risk Factors; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D051759:Xeroderma Pigmentosum Group D Protein / Q000235:genetics*
chemical_list: D025521:Tumor Suppressor Proteins; C093713:ribonucleotide reductase M2; C475286:RRM1 protein, human; D012262:Ribonucleoside Diphosphate Reductase; D051759:Xeroderma Pigmentosum Group D Protein; C497292:ERCC2 protein, human
keywords: CAD; ERCC2; RRM1; RRM2; polymorphism