title: The paradoxical association of common polymorphisms of the renin-angiotensin system genes with risk of myocardial infarction.
abstract: BACKGROUND
  The insertion/deletion polymorphism of the angiotensin-converting enzyme (ACE) and the A1166C polymorphism of the angiotensin-II AT1 receptor (AT1R) have been extensively investigated as possible risk factors for myocardial infarction (MI).
  
  
  METHODS
  Genetic association, case-control study, specifically designed to investigate the association of the above-mentioned polymorphisms with risk of MI in a homogeneous, low coronary risk, Caucasian population. The study population consisted of 1603 consecutive patients with acute MI who were recruited from nine clinics, located in three cities, and 699 unrelated adults who were randomly selected from the city catalogues.
  
  
  RESULTS
  In univariate analysis, the DD genotype was found to be more prevalent among controls (40.8 vs. 35.2%, P=0.011). In multivariate analysis adjusted for age, gender, smoking status, diabetes mellitus, hypercholesterolaemia, hypertension and family history of coronary artery disease, the presence of the DD genotype was independently and negatively associated with risk of AMI (RR=0.743, 95% CI=0.595-0.927, P=0.008). The CC genotype was not found to be significantly associated with risk of MI, either in univariate (6.2 vs. 6.4%, P=0.856), or in multivariate analysis adjusted for the same confounders (RR=0.743, 95% CI=0.473-1.167, P=0.197).
  
  
  CONCLUSIONS
  Contrary to previous reports, in this study the DD genotype of the ACE gene, but not the CC genotype of the AT1R gene, was associated with a lower risk of MI. Our results emphasize the complexity of genotype-phenotype interactions in the pathogenesis of ischaemic heart disease and question the previously hypothesized role of the DD genotype on risk of acute myocardial infarction.
authors.affiliation: First Cardiac Department, Evangelismos Hospital, Athens, Greece. geomabuz@otenet.gr
authors.forename: George K
authors.initials: GK
authors.lastname: Andrikopoulos
authors.forename: Dimitri J
authors.initials: DJ
authors.lastname: Richter
authors.forename: Edward W
authors.initials: EW
authors.lastname: Needham
authors.forename: Stylianos E
authors.initials: SE
authors.lastname: Tzeis
authors.forename: Michalis N
authors.initials: MN
authors.lastname: Zairis
authors.forename: Elias J
authors.initials: EJ
authors.lastname: Gialafos
authors.forename: Paraskeui G
authors.initials: PG
authors.lastname: Vogiatzi
authors.forename: Evaggelos G
authors.initials: EG
authors.lastname: Papasteriadis
authors.forename: Fotios G
authors.initials: FG
authors.lastname: Kardaras
authors.forename: Stefanos G
authors.initials: SG
authors.lastname: Foussas
authors.forename: John E
authors.initials: JE
authors.lastname: Gialafos
authors.forename: Christodoulos I
authors.initials: CI
authors.lastname: Stefanadis
authors.forename: Pavlos K
authors.initials: PK
authors.lastname: Toutouzas
authors.forename: Raj K
authors.initials: RK
authors.lastname: Mattu
mesh_terms: D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006115:Greece; D006801:Humans; D006937:Hypercholesterolemia / Q000235:genetics; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009203:Myocardial Infarction / Q000235:genetics*; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D011110:Polymorphism, Genetic; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics*; D012307:Risk Factors; D044465:White People / Q000235:genetics
chemical_list: D044140:Receptor, Angiotensin, Type 1; D007703:Peptidyl-Dipeptidase A