title: Angiotensin-converting enzyme and angiotensin II receptor 1 polymorphisms: association with early coronary disease.
abstract: OBJECTIVE
  To examine the association between coronary artery disease and polymorphisms at the angiotensin-converting enzyme (ACE) and angiotensin II type 1 receptor (AT1R) genes.
  
  
  METHODS
  A total of 181 patients younger than 50 years and 240 controls from the same homogeneous Caucasian population (Asturias, Northern Spain) were genotyped (using polymerase chain reaction) for the ACE insertion/deletion (ACE-I/D) and the AT1R A/C transversion (AT1R-A/C) (3-untranslated region) polymorphisms.
  
  
  RESULTS
  The DD-genotype was at a non-significant higher frequency among patients (50%) than in controls (41%). No difference between the two groups was found for the AT1R-genotypes. Distribution of ACE-genotypes according to AT1R-genotypes showed a significant association between ACE-DD and AT1R-CC and early coronary disease. Among the CC patients 58% were DD, compared to 21% among the controls (p = 0.02; OR = 5.32, 95% CI = 1.45, 19.51). We determined the distribution of these genotypes among the hypertensive and non-hypertensive patients. Frequencies of ACE- or AT1R-genotypes did not differ between the two groups. However, we found an interaction between the DD- and CC-genotypes in the group of normotensives. Among the CC patients, 13% of the hypertensives and 75% of the normotensives were DD (p = 0.014).
  
  
  CONCLUSIONS
  Our results indicate a synergistic contribution of ACE and AT1R polymorphisms to the risk of coronary artery disease. This gene-gene interaction could have clinical implications. Approximately 2% of individuals in our population are CC + DD, and the genotyping of both polymorphisms could identify those with a high relative risk for coronary artery disease.
authors.affiliation: Instituto Reina Sofía de Investigación Nefrológica-Laboratorio de Genética Molecular, Hospital Central de Asturias, Oviedo, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Alvarez
authors.forename: J R
authors.initials: JR
authors.lastname: Reguero
authors.forename: A
authors.initials: A
authors.lastname: Batalla
authors.forename: G
authors.initials: G
authors.lastname: Iglesias-Cubero
authors.forename: A
authors.initials: A
authors.lastname: Cortina
authors.forename: V
authors.initials: V
authors.lastname: Alvarez
authors.forename: E
authors.initials: E
authors.lastname: Coto
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D003327:Coronary Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000235:genetics*; D012306:Risk
chemical_list: D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D007703:Peptidyl-Dipeptidase A