title: Contribution of deletion in angiotensin-converting enzyme but not A1166C angiotensin II type-1 receptor gene polymorphisms to clinical outcomes in atherothrombotic disease.
abstract: OBJECTIVE
  Angiotensin-converting enzyme insertion/deletion (rs4340) and angiotensin II type 1 receptor A1166C (rs5186) gene polymorphisms may be involved in coronary heart disease (CHD). This study was designed to evaluate potential relationships between these polymorphisms and the risk of long-term all-cause mortality and major adverse cardiovascular events (MACE) in patients requiring revascularization for atherothrombotic disease (ATD) lesions.
  
  
  METHODS
  This prospective observational study concerned patients referred for supra-aortic vessel disease (SVD), CHD, peripheral artery occlusive disease (PAOD) or visceral artery disease (VAD). Collected data included ATD referral site, ATD symptoms, personal and familial medical histories, ATD extent, vascular risk factors, biological values, medication use and rs4340 and rs5186 polymorphisms. The primary end point was all-cause mortality. The secondary end point, MACE, included cardiovascular death, clinical ischemic event related to SVD, CHD, PAOD or VAD.
  
  
  RESULTS
  The cohort comprised 956 patients of whom 872 (91.2%) were genotyped and followed for 21.1 ± 9.9 months. Patients were referred for SVD (25.9%), CHD (42.3%), PAOD (35.2%) or VAD (1.6%). All-cause mortality and MACE rates were 7.6 and 27.2%, respectively. When comparing I/D + D/D vs. I/I genotypes, rs4340 polymorphism was associated with higher all-cause mortality rates according to uni- and multivariate analyses (p=0.008 and 0.011, respectively). Other differences were not significant (rs4340 polymorphism and MACE, rs5186 polymorphism and all-cause mortality and MACE). No interaction was found between the polymorphisms. Other independent predictors of all-cause mortality included PAOD history, SVD history, body mass index <25 kg/m(2), HbA(1c) ≥6.5%, absence of dyslipidemia and no use of aspirin.
  
  
  CONCLUSIONS
  rs4340 polymorphism is associated with long-term all-cause mortality in advanced ATD patients requiring revascularization, whereas rs5186 polymorphism does not.
authors: Vascular Medicine, CHU of Caen, Caen Cedex, France. lehello-c@chu-caen.fr
authors: Claire
authors: C
authors: Le Hello
authors: Sabine
authors: S
authors: Fradin
authors: Rémy
authors: R
authors: Morello
authors: Olivier
authors: O
authors: Coffin
authors: Dominique
authors: D
authors: Maïza
authors: Martial
authors: M
authors: Hamon
mesh_terms: D000368:Aged; D001018:Aortic Diseases / Q000235:genetics / Q000401:mortality / Q000601:surgery; D001157:Arterial Occlusive Diseases / Q000235:genetics / Q000401:mortality / Q000601:surgery; D004252:DNA Mutational Analysis; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D054643:INDEL Mutation; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D058729:Peripheral Arterial Disease / Q000235:genetics / Q000401:mortality / Q000601:surgery; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D011446:Prospective Studies; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics*; D014652:Vascular Diseases / Q000235:genetics* / Q000401:mortality / Q000601:surgery; D058017:Vascular Grafting
chemical_list: C544065:AGTR1 protein, human; D044140:Receptor, Angiotensin, Type 1; D007703:Peptidyl-Dipeptidase A