title: Synergistic association of DNA repair relevant gene polymorphisms with the risk of coronary artery disease in northeastern Han Chinese.
abstract: Evidence is mounting suggesting that DNA damage is implicated in the development and progression of atherosclerosis. To yield more information, we focused on six well-characterized polymorphisms from four DNA repair-relevant candidate genes, viz. XRCC1 (rs1799782 and rs25487), XRCC3 (rs861539), MTHFR (rs1801133 and rs4846049), and NQO1 (rs1800566), to identify and characterize their potential gene-to-gene interactions in susceptibility to coronary artery disease (CAD) in Han Chinese. This was a hospital-based case-control study involving 1142 patients diagnosed with CAD and 1106 age- and gender-matched controls. All participants were angiographically confirmed. Risk estimates were expressed as odds ratio (OR) and 95% confidence interval (95% CI). All six examined polymorphisms met Hardy-Weinberg equilibrium. Overall there were significant differences in the genotype/allele distributions of MTHFR gene rs1801133 and rs4846049 (both P ≤ 0.005), and in the genotype distributions of XRCC1 gene rs1799782 (P = 0.002) between patients and controls. The adjusted risk of having CAD was more evident for rs1799782 (OR = 1.53; 95% CI: 1.16-2.02; P = 0.003), rs1801133 (OR = 1.54; 95% CI: 1.22-1.94; P < 0.001), and rs4846049 (OR = 1.74; 95% CI: 1.13-2.69; P = 0.013) under the recessive model. Interaction analyses indicated that the overall best multifactor dimensionality reduction (MDR) model included rs4846049, rs1801133, and rs1799782, and this model had a maximal testing accuracy of 0.6885 and a cross-validation consistency of 10 out of 10 (P = 0.0030). Further interaction entropy graph bore out the validity of this MDR model. Taken together, our findings demonstrate a contributory role of genetic defects in XRCC1 and MTHFR genes, both individually and interactively, in the development of CAD in Han Chinese.
authors: Dalian Medical University, Dalian, Liaoning, China; Department of Cardiology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China.
authors: Xiaohong
authors: X
authors: Yu
authors: Department of Cardiology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China.
authors: Jun
authors: J
authors: Liu
authors: Department of Cardiology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China.
authors: Hao
authors: H
authors: Zhu
authors: Department of Cardiology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China.
authors: Yunlong
authors: Y
authors: Xia
authors: Department of Cardiology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China.
authors: Lianjun
authors: L
authors: Gao
authors: Department of Cardiology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China.
authors: Yingxue
authors: Y
authors: Dong
authors: Department of Hypertension, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors: Nan
authors: N
authors: Jia
authors: Department of Cardiology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors: Weifeng
authors: W
authors: Shen
authors: Department of Cardiology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China. Electronic address: yyz_heart@163.com.
authors: Yanzong
authors: Y
authors: Yang
authors: State Key Laboratory of Medical Genomics, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Shanghai Institute of Hypertension, Shanghai, China. Electronic address: niuwenquan_shcn@163.com.
authors: Wenquan
authors: W
authors: Niu
mesh_terms: D000368:Aged; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D003324:Coronary Artery Disease / Q000453:epidemiology / Q000235:genetics*; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics; D008875:Middle Aged; D011110:Polymorphism, Genetic; D000076105:X-ray Repair Cross Complementing Protein 1
chemical_list: D004268:DNA-Binding Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2)
keywords: Coronary artery disease; DNA repair; Gene-to-gene interaction; Polymorphism