title: Genotypic interactions of renin-angiotensin system genes in myocardial infarction.
abstract: BACKGROUND
  Three-gene interactions among the genetic polymorphisms of the renin-angiotensin system (RAS) associated with acute myocardial infarction (AMI) have not been examined in a single population. We hypothesized that all types of gene-to-gene associations may occur in AMI, but that some will have a higher risk, depending on the gene frequencies.
  
  
  METHODS
  Polymorphisms of the AGT (M235T), ACE (I/D) and AGTR1 (A1166C) genes in AMI patients and controls were analyzed using the polymerase chain reaction. Classic coronary risk factors were analyzed in all individuals.
  
  
  RESULTS
  Logistic regression analysis of these factors and the genetic polymorphisms demonstrated that smoking, family history of CAD, arterial hypertension and total cholesterol were the most significant contributors to AMI. The genotypic frequencies for all three genes alone were similar between the infarction and control groups, with no increased risk of developing AMI. Double homozygous combinations for normal alleles (MM of AGT, II of ACE and AA of AGTR1) had a lower risk of AMI (odds ratio<0.38), indicating a protective effect in these individuals. In genotypic combinations that included at least one unfavorable allele, the risk (odds ratio) of developing AMI was 2.92, 2.63 and 2.68 for AGT vs. ACE, AGT vs. ATR1 and ACE vs. AGTR1, respectively. The positive interaction among the three genes and the risk of AMI had an odds ratio of 3.78 with a 95% CI of 0.88-12.85.
  
  
  CONCLUSIONS
  The risk of developing AMI is higher whenever there are unfavorable alleles in gene-to-gene associations in the RAS.
authors.affiliation: Department of Internal Medicine, Medical School, Federal University of Uberlândia, Brazil. messiasaa@bol.com.br
authors.forename: Messias Antônio
authors.initials: MA
authors.lastname: Araújo
authors.forename: Luiz Ricardo
authors.initials: LR
authors.lastname: Goulart
authors.forename: Elisângela Rosa
authors.initials: ER
authors.lastname: Cordeiro
authors.forename: Renata Ríspoli
authors.initials: RR
authors.lastname: Gatti
authors.forename: Bruno Soares
authors.initials: BS
authors.lastname: Menezes
authors.forename: Clauber
authors.initials: C
authors.lastname: Lourenço
authors.forename: Heyder Diniz
authors.initials: HD
authors.lastname: Silva
mesh_terms: D000293:Adolescent; D000483:Alleles; D000808:Angiotensinogen / Q000097:blood / Q000235:genetics*; D015415:Biomarkers / Q000097:blood; D004247:DNA / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D009154:Mutation; D009203:Myocardial Infarction / Q000097:blood / Q000235:genetics*; D016017:Odds Ratio; D007703:Peptidyl-Dipeptidase A / Q000097:blood / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D044140:Receptor, Angiotensin, Type 1 / Q000097:blood / Q000235:genetics*; D012084:Renin-Angiotensin System / Q000235:genetics*; D012307:Risk Factors
chemical_list: D015415:Biomarkers; D044140:Receptor, Angiotensin, Type 1; D000808:Angiotensinogen; D004247:DNA; D007703:Peptidyl-Dipeptidase A