title: Gene-gene interactions in renin-angiotensin-aldosterone system contributes to end-stage renal disease susceptibility in a Han Chinese population.
abstract: OBJECTIVE
  In this study, we investigated whether RAAS gene single nucleotide polymorphisms (SNPs) and their interactions were associated with end-stage renal stage (ESRD).
  
  
  RESULTS
  This was a case-control study for 647 ESRD cases and 644 controls. AGT (M235T (rs699) and T174M (rs4762)), AGTR1 (A1166C (rs5186) and C573T (rs5182)), ACE (I/D (rs1799752) and G2350A (rs4343)), and CYP11B2 C-344T (rs1799998) were genotyped and compared between cases and controls to identify SNPs associated with ESRD susceptibility. Multifactor dimensionality reduction (MDR) was used to identify gene-gene interactions. Several RAAS genes were associated with ESRD: AGT M235T, ACE I/D, ACE G2350A, and CYP11B2 C-344T. By MDR analysis, a three-locus model (ACE ID/ACE G2350A/CYP11B2 C-344T) of gene-gene interaction was the best for predicting ESRD risk, and its maximum testing accuracy was 56.08% and maximum cross-validation consistency was 9/10. ESRD risk was higher with the simultaneous occurrence of ACE I/D DD-ACE G2350A AA. AGT, ACE, and CYP11B2 gene polymorphisms are associated with ESRD.
  
  
  CONCLUSIONS
  The gene-gene interaction effects of ACE I/D, ACE G2350A, and CYP11B2 C-344T polymorphisms are more important than individual factors for ESRD development among Han Chinese.
authors: School of Public Health, National Defense Medical Center, Taipei, Taiwan.
authors: Sui-Lung
authors: SL
authors: Su
authors: School of Public Health, National Defense Medical Center, Taipei, Taiwan.
authors: Hsin-Yi
authors: HY
authors: Yang
authors: Division of Nephrology, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors: Chia-Chao
authors: 0000-0002-8772-011X
authors: CC
authors: Wu
authors: Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors: Herng-Sheng
authors: HS
authors: Lee
authors: Division of Nephrology, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan ; Division of Nephrology, Department of Medicine, Shuang Ho Hospital, Graduate Institute of Clinical Medicine, Taipei Medical University, New Taipei City, Taiwan.
authors: Yuh-Feng
authors: YF
authors: Lin
authors: School of Public Health, National Defense Medical Center, Taipei, Taiwan.
authors: Chi-An
authors: CA
authors: Hsu
authors: School of Public Health, National Defense Medical Center, Taipei, Taiwan.
authors: Ching-Huang
authors: CH
authors: Lai
authors: Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan.
authors: Chin
authors: C
authors: Lin
authors: School of Public Health, National Defense Medical Center, Taipei, Taiwan.
authors: Sen-Yeong
authors: SY
authors: Kao
authors: Division of Nephrology, Department of Medicine, Cardinal Tien Hospital, School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan.
authors: Kuo-Cheng
authors: KC
authors: Lu
mesh_terms: D019405:Cytochrome P-450 CYP11B2 / Q000235:genetics*; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D006801:Humans; D007676:Kidney Failure, Chronic / Q000453:epidemiology* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D015995:Prevalence; D025941:Protein Interaction Mapping / Q000706:statistics & numerical data*; D012084:Renin-Angiotensin System / Q000235:genetics*; D015203:Reproducibility of Results; D012307:Risk Factors; D012680:Sensitivity and Specificity; D013624:Taiwan / Q000453:epidemiology
chemical_list: D005819:Genetic Markers; D019405:Cytochrome P-450 CYP11B2; D007703:Peptidyl-Dipeptidase A