title: Effect of ACE insertion/deletion and 12 other polymorphisms on clinical outcomes and response to treatment in the LIFE study.
abstract: OBJECTIVE
  This pharmacogenetics substudy from the Losartan Intervention for Endpoint reduction in Hypertension study in patients with hypertension and left ventricular hypertrophy (LVH) treated with the angiotensin receptor blocker losartan versus the beta-blocker atenolol for 4.8 years tested whether the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene and 12 other previously well-characterized polymorphisms of hypertension susceptibility genes affected blood pressure reduction, heart rate reduction, cardiovascular events, and/or response to treatment. These polymorphisms were chosen because they could affect blood pressure control or the pharmacological action of losartan or atenolol.
  
  
  METHODS
  We genotyped 3503 patients, 1774 on losartan and 1729 on atenolol.
  
  
  RESULTS
  ACE and the 12 other genotypes did not affect the reduction in systolic blood pressure, diastolic blood pressure, pulse pressure, mean arterial pressure, or heart rate, or treatment differences between losartan and atenolol on these endpoints, as assessed by general linear models. Also, ACE and the 12 other genotypes did not affect risk of the primary composite endpoint or its components stroke, myocardial infarction, and cardiovascular death, or treatment differences between losartan and atenolol on these endpoints, as assessed by Cox proportional hazards models including baseline Framingham risk score and LVH.
  
  
  CONCLUSIONS
  ACE insertion/deletion and 12 other polymorphisms of hypertension susceptibility genes did not affect blood pressure reduction, heart rate reduction, or cardiovascular events in patients with hypertension and LVH, or treatment differences between losartan and atenolol on these endpoints. These results suggest that the observed effects of losartan versus atenolol in the Losartan Intervention for Endpoint reduction in hypertension study do not depend on ACE and 12 other polymorphisms of hypertension susceptibility genes.
authors.affiliation: Department of Clinical Biochemistry, Herlev University Hospital, University of Copenhagen, Herlev, Denmark. brno@heh.regionh.dk
authors.forename: Børge G
authors.initials: BG
authors.lastname: Nordestgaard
authors.forename: Kimmo
authors.initials: K
authors.lastname: Kontula
authors.forename: Marianne
authors.initials: M
authors.lastname: Benn
authors.forename: Björn
authors.initials: B
authors.lastname: Dahlöf
authors.forename: Ulf
authors.initials: U
authors.lastname: de Faire
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Edelman
authors.forename: Erik
authors.initials: E
authors.lastname: Eliasson
authors.forename: Frej
authors.initials: F
authors.lastname: Fyhrquist
authors.forename: Darcy A
authors.initials: DA
authors.lastname: Hille
authors.forename: Hans
authors.initials: H
authors.lastname: Ibsen
authors.forename: Paulette A
authors.initials: PA
authors.lastname: Lyle
authors.forename: Kåre
authors.initials: K
authors.lastname: Berg
authors.forename: Mia
authors.initials: M
authors.lastname: Sandberg
authors.forename: Amar A
authors.initials: AA
authors.lastname: Sethi
authors.forename: Peggy H
authors.initials: PH
authors.lastname: Wong
authors.forename: Ingrid
authors.initials: I
authors.lastname: Os
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D023381:Endpoint Determination; D005260:Female; D005838:Genotype; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D017379:Hypertrophy, Left Ventricular / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D054643:INDEL Mutation / Q000235:genetics*; D019808:Losartan / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics* / Q000378:metabolism*; D011110:Polymorphism, Genetic; D016896:Treatment Outcome
chemical_list: D000959:Antihypertensive Agents; D007703:Peptidyl-Dipeptidase A; D019808:Losartan