title: Genetic variation-optimized treatment benefit of angiotensin-converting enzyme inhibitors in patients with stable coronary artery disease: a 12-year follow-up study.
abstract: OBJECTIVE
  The objective of this study was to examine the relationship between renin-angiotensin system genotypes and the pharmacogenetics of angiotensin-converting enzyme (ACE) inhibitors in Chinese patients with coronary artery disease (CAD).
  
  
  METHODS
  Patients with angiographic CAD were recruited from 1995 to 2003. The baseline characteristics and genetic polymorphisms [ACE gene insertion/deletion (I/D) polymorphisms, six polymorphisms of the angiotensinogen (AGT) gene, and A-1166C polymorphisms of the angiotensin-II type I receptor gene (AGT1R)] were established. Patients were divided into two groups (ACE inhibitor or no ACE inhibitor) and followed for up to 12 years. Kaplan-Meier curves and Cox regression models were used to determine the survival and major cardiovascular events (MACE) event-free survival trends. Pharmacogenetic effects were determined by several Cox regression models.
  
  
  RESULTS
  Of the 784 patients, 432 were treated with ACE inhibitors and 352 were not. ACE inhibitors were associated with a lower MACE rate at 4000 days. In addition, the ACE I/D gene D and AGT1R gene C alleles were associated with a higher MACE rate on the basis of a multivariate regression analysis. This effect was attenuated by the pharmacogenetic interaction of ACE inhibitors and the ACE gene (ACE inhibitors* ACE gene, hazard ratio: 0.8, 95% confidence interval: 0.62-0.94, P=0.03).
  
  
  CONCLUSIONS
  ACE inhibitors were associated with a significant decrease in MACE in Chinese patients diagnosed with CAD. Genetic variants were also associated with event-free survival, but their effects were modified by the use of ACE inhibitors.
authors: Department of Clinical Pathology, Cardiovascular Center, Far Eastern Memorial Hospital, New Taipei City, Taiwan.
authors: Jen-Kuang
authors: JK
authors: Lee
authors: Cho-Kai
authors: CK
authors: Wu
authors: Chia-Ti
authors: CT
authors: Tsai
authors: Lian-Yu
authors: LY
authors: Lin
authors: Jou-Wei
authors: JW
authors: Lin
authors: Kuo-Liong
authors: KL
authors: Chien
authors: Juey-Jen
authors: JJ
authors: Hwang
authors: Chunn-Lee
authors: CL
authors: Lin
authors: Chuen-Den
authors: CD
authors: Tseng
authors: Fu-Tien
authors: FT
authors: Chiang
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage*; D003324:Coronary Artery Disease / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D011110:Polymorphism, Genetic; D016016:Proportional Hazards Models; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics*; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000235:genetics
chemical_list: C544065:AGTR1 protein, human; D000806:Angiotensin-Converting Enzyme Inhibitors; D044140:Receptor, Angiotensin, Type 1; D007703:Peptidyl-Dipeptidase A