title: Genetic variation in the renin--angiotensin system, use of renin--angiotensin system inhibitors and the risk of myocardial infarction.
abstract: BACKGROUND
  This study investigated whether variation in the genes encoding for ACE, AGT and AGTR1 modifies the risk of myocardial infarction (MI) related to ACE inhibitors and AT II antagonists.
  
  
  METHODS
  A nested case-control study among users of antihypertensive drugs, in whom the polymorphisms ACE-G4656C, ACE-T3892C, AGT-C235T and AGTR1-A1166C were genotyped.
  
  
  RESULTS
  Among 613 cases and 3630 controls, the risk of MI was significantly lower among users of ACE inhibitors compared with that in users of other antihypertensives (adjusted OR, 0.78; 95% CI, 0.63-0.97). In patients using ACE inhibitors the largest risk reduction was found in patients carrying the ACE-4656-G allele (GC and GG genotypes) compared with patients carrying the CC genotype (OR, 0.68; 95% CI, 0.53-0.86 and OR, 1.26, 95% CI, 0.78-2.02, respectively). The synergy index for this interaction was statistically significant (SI, 0.58; 95% CI, 0.35-0.95). The risk of MI was reduced in those who were current users of ACE inhibitors those who had been prescribed dosages lower than the equivalent of 1 defined daily dose (DDD) and those having the AGTR1-1166AC or AA genotype compared with that in users of ACE inhibitors with the AGTR1-1166CC genotype (SI, 3.67; 95% CI,1.18-11.4). None of the polymorphisms modified the effectiveness of AT II antagonists regarding the risk of MI.
  
  
  CONCLUSIONS
  This study shows an interaction between the use of ACE inhibitors and ACE-G4656C polymorphism, and in low doses also with AGTR1-A1166C polymorphism, in the prevention of MI.
authors.affiliation: Department of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences (UIPS), University of Utrecht, Utrecht, the Netherlands.
authors.forename: Anke-Hilse
authors.initials: AH
authors.lastname: Maitland-van der Zee
authors.forename: Diane Bma
authors.initials: DB
authors.lastname: van Wieren-de Wijer
authors.forename: Anthonius
authors.initials: A
authors.lastname: de Boer
authors.forename: Abraham A
authors.initials: AA
authors.lastname: Kroon
authors.forename: Peter W
authors.initials: PW
authors.lastname: de Leeuw
authors.forename: Paul
authors.initials: P
authors.lastname: Schiffers
authors.forename: Rob Gjh
authors.initials: RG
authors.lastname: Janssen
authors.forename: Bruce M
authors.initials: BM
authors.lastname: Psaty
authors.forename: Cornelia M
authors.initials: CM
authors.lastname: van Duijn
authors.forename: Bruno Hch
authors.initials: BH
authors.lastname: Stricker
authors.forename: Olaf H
authors.initials: OH
authors.lastname: Klungel
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012084:Renin-Angiotensin System / Q000235:genetics*; D012307:Risk Factors
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors