title: Angiotensin II type 2 receptor gene polymorphism and cardiovascular phenotypes: the GLAECO and GLAOLD studies.
abstract: BACKGROUND
  The angiotensin II type 2 (AT2) receptor is thought to play a role in cardiovascular disorders such as neointima formation after vascular injury, cardiac hypertrophy and myocardial infarction (MI). Recently, the biallelic polymorphism G + 1675A in intron 1 of the AT2 receptor gene has been associated with left ventricular posterior, septal and relative wall thickness, as well as left ventricular mass index in young hypertensive males.
  
  
  METHODS
  To investigate its potential role in left ventricular hypertrophy (LVH) and other cardiovascular traits, 1968 individuals from two population samples (the Glasgow Heart Scan, GLAECO and Glasgow Heart Scan Old, GLAOLD studies) with echocardiographically and electrocardiographically assessed phenotypes, were genotyped for G + 1675A using allele-specific oligonucleotide hybridization. Both studies had a similar design, only the age-ranges differed, being 25-74 years in the GLAECO study and 55-74 years in the GLAOLD study, so that internal consistency of results could also be assessed. Since the AT2 gene is located on the X chromosome, males and females were analysed separately.
  
  
  RESULTS
  The + 1675A allele frequency was 0.49 and 0.51, in the GLAECO and GLAOLD studies, respectively. In both studies, the genotype frequencies were similar in hypertensive and non-hypertensive individuals. In the GLAOLD study, in females with episodes of coronary ischemia and MI, the AT2 + 1675A allele was more common than in females with no episode (86.5% vs. 73.5%, respectively; P < 0.007). This effect was not observed in males. In the same study, AT2 + 1675A allele carriers were more common in males with LVH, than in those without LVH (60.3% vs. 46.0%, respectively; P = 0.047). This result was unchanged after exclusion of subjects taking antihypertensive drugs (including ACE inhibitors) (64.4% vs. 47.4%, P = 0.038). However, in the GLAECO study, these results could not be replicated, even when subjects > 55 years of age were considered separately.
  
  
  CONCLUSIONS
  Our study gives rise to a potential implication of the AT2 G + 1675A polymorphism in LVH and coronary ischemia subgroups. Since these results were not consistent in both studies, but are partially in agreement with two independent investigations, further efforts should be made to elucidate the specific nature of these genotype/phenotype interactions.
authors.affiliation: Institute of Clinical Pharmacology and Toxicology, Department of Clinical Pharmacology, Benjamin Franklin Medical Center, Freie Universität Berlin, Hindenburgdamm 30, 12200 Berlin, Germany. herrmann@medizin.fu-berlin.de
authors.forename: Stefan-Martin
authors.initials: SM
authors.lastname: Herrmann
authors.forename: Viviane
authors.initials: V
authors.lastname: Nicaud
authors.forename: Klaus
authors.initials: K
authors.lastname: Schmidt-Petersen
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Pfeifer
authors.forename: Jeanette
authors.initials: J
authors.lastname: Erdmann
authors.forename: Theresa
authors.initials: T
authors.lastname: McDonagh
authors.forename: Henry J
authors.initials: HJ
authors.lastname: Dargie
authors.forename: Martin
authors.initials: M
authors.lastname: Paul
authors.forename: Vera
authors.initials: V
authors.lastname: Regitz-Zagrosek
mesh_terms: D017677:Age Distribution; D000368:Aged; D001483:Base Sequence; D015331:Cohort Studies; D003324:Coronary Artery Disease / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000453:epidemiology / Q000235:genetics*; D017379:Hypertrophy, Left Ventricular / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011336:Probability; D011379:Prognosis; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000235:genetics*; D018570:Risk Assessment; D012494:Sampling Studies; D017678:Sex Distribution
chemical_list: D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin