title: Pharmacogenetic association of the angiotensin-converting enzyme insertion/deletion polymorphism on blood pressure and cardiovascular risk in relation to antihypertensive treatment: the Genetics of Hypertension-Associated Treatment (GenHAT) study.
abstract: BACKGROUND
  Previous studies have reported that blood pressure response to antihypertensive medications is influenced by genetic variation in the renin-angiotensin-aldosterone system, but no clinical trails have tested whether the ACE insertion/deletion (I/D) polymorphism modifies the association between the type of medication and multiple cardiovascular and renal phenotypes.
  
  
  RESULTS
  We used a double-blind, active-controlled randomized trial of antihypertensive treatment that included hypertensives > or =55 years of age with > or =1 risk factor for cardiovascular disease. ACE I/D genotypes were determined in 37 939 participants randomized to chlorthalidone, amlodipine, lisinopril, or doxazosin treatments and followed up for 4 to 8 years. Primary outcomes included fatal coronary heart disease (CHD) and/or nonfatal myocardial infarction. Secondary outcomes included stroke, all-cause mortality, combined CHD, and combined cardiovascular disease. Fatal and nonfatal CHD occurred in 3096 individuals during follow-up. The hazard rates for fatal and nonfatal CHD and the secondary outcomes were similar across antihypertensive treatments. ACE I/D genotype group was not associated with fatal and nonfatal CHD (relative risk of DD versus ID and II, 0.99; 95% CI, 0.91 to 1.07) or any secondary outcome. The 6-year hazard rate for fatal and nonfatal CHD in the DD genotype group was not statistically different from the ID and II genotype group by type of treatment. No secondary outcome measure was statistically different across antihypertensive treatment and ACE I/D genotype strata.
  
  
  CONCLUSIONS
  ACE I/D genotype group was not a predictor of CHD, nor did it modify the response to antihypertensive treatment. We conclude that the ACE I/D polymorphism is not a useful marker to predict antihypertensive treatment response.
authors.affiliation: University of Minnesota, Division of Epidemiology, Minneapolis, USA. arnett@ms.soph.uab.edu
authors.forename: Donna K
authors.initials: DK
authors.lastname: Arnett
authors.forename: Barry R
authors.initials: BR
authors.lastname: Davis
authors.forename: Charles E
authors.initials: CE
authors.lastname: Ford
authors.forename: Eric
authors.initials: E
authors.lastname: Boerwinkle
authors.forename: Cathie
authors.initials: C
authors.lastname: Leiendecker-Foster
authors.forename: Michael B
authors.initials: MB
authors.lastname: Miller
authors.forename: Henry
authors.initials: H
authors.lastname: Black
authors.forename: John H
authors.initials: JH
authors.lastname: Eckfeldt
mesh_terms: D000368:Aged; D017311:Amlodipine / Q000008:administration & dosage / Q000494:pharmacology; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects* / Q000235:genetics; D002318:Cardiovascular Diseases / Q000209:etiology*; D002752:Chlorthalidone / Q000008:administration & dosage / Q000494:pharmacology; D004311:Double-Blind Method; D017292:Doxazosin / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D017706:Lisinopril / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D000959:Antihypertensive Agents; D017311:Amlodipine; D017706:Lisinopril; D007703:Peptidyl-Dipeptidase A; D017292:Doxazosin; D002752:Chlorthalidone