title: Adrenergic gene polymorphisms and cardiovascular risk in the NHLBI-sponsored Women's Ischemia Syndrome Evaluation.
abstract: BACKGROUND
  Adrenergic gene polymorphisms are associated with cardiovascular and metabolic phenotypes. We investigated the influence of adrenergic gene polymorphisms on cardiovascular risk in women with suspected myocardial ischemia.
  
  
  METHODS
  We genotyped 628 women referred for coronary angiography for eight polymorphisms in the alpha1A-, beta1-, beta2- and beta3-adrenergic receptors (ADRA1A, ADRB1, ADRB2, ADRB3, respectively), and their signaling proteins, G-protein beta 3 subunit (GNB3) and G-protein alpha subunit (GNAS). We compared the incidence of death, myocardial infarction, stroke, or heart failure between genotype groups in all women and women without obstructive coronary stenoses.
  
  
  RESULTS
  After a median of 5.8 years of follow-up, 115 women had an event. Patients with the ADRB1 Gly389 polymorphism were at higher risk for the composite outcome due to higher rates of myocardial infarction (adjusted hazard ratio [HR] 3.63, 95% confidence interval [95%CI] 1.17-11.28; Gly/Gly vs. Arg/Arg HR 4.14, 95%CI 0.88-19.6). The risk associated with ADRB1 Gly389 was limited to those without obstructive CAD (n = 400, Pinteraction = 0.03), albeit marginally significant in this subset (HR 1.71, 95%CI 0.91-3.19). Additionally, women without obstructive CAD carrying the ADRB3 Arg64 variant were at higher risk for the composite endpoint (HR 2.10, 95%CI 1.05-4.24) due to subtle increases in risk for all of the individual endpoints. No genetic associations were present in women with obstructive CAD.
  
  
  CONCLUSIONS
  In this exploratory analysis, common coding polymorphisms in the beta1- and beta3-adrenergic receptors increased cardiovascular risk in women referred for diagnostic angiography, and could improve risk assessment, particularly for women without evidence of obstructive CAD.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00000554.
authors.affiliation: Department of Pharmacy Practice and Center for Pharmacogenomics, University of Florida College of Pharmacy, Gainesville, FL, USA. pacanow@cop.ufl.edu
authors.forename: Michael A
authors.initials: MA
authors.lastname: Pacanowski
authors.forename: Issam
authors.initials: I
authors.lastname: Zineh
authors.forename: Haihong
authors.initials: H
authors.lastname: Li
authors.forename: B Delia
authors.initials: BD
authors.lastname: Johnson
authors.forename: Rhonda M
authors.initials: RM
authors.lastname: Cooper-DeHoff
authors.forename: Vera
authors.initials: V
authors.lastname: Bittner
authors.forename: Dennis M
authors.initials: DM
authors.lastname: McNamara
authors.forename: Barry L
authors.initials: BL
authors.lastname: Sharaf
authors.forename: C Noel Bairey
authors.initials: CN
authors.lastname: Merz
authors.forename: Carl J
authors.initials: CJ
authors.lastname: Pepine
authors.forename: Julie A
authors.initials: JA
authors.lastname: Johnson
mesh_terms: D000368:Aged; D002318:Cardiovascular Diseases / Q000235:genetics* / Q000401:mortality*; D002864:Chromogranins; D002986:Clinical Trials as Topic; D005260:Female; D005500:Follow-Up Studies; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics; D005787:Gene Frequency; D005838:Genotype; D020962:Heterotrimeric GTP-Binding Proteins / Q000235:genetics; D006801:Humans; D053208:Kaplan-Meier Estimate; D016015:Logistic Models; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000235:genetics / Q000401:mortality; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D044469:Racial Groups; D011941:Receptors, Adrenergic / Q000235:genetics*; D018342:Receptors, Adrenergic, beta-1 / Q000235:genetics; D022702:Receptors, Adrenergic, beta-3 / Q000235:genetics; D012307:Risk Factors
chemical_list: D002864:Chromogranins; C454420:G-protein beta3 subunit; D008565:Membrane Proteins; D011941:Receptors, Adrenergic; D018342:Receptors, Adrenergic, beta-1; D022702:Receptors, Adrenergic, beta-3; C406732:GNAS protein, human; D019205:GTP-Binding Protein alpha Subunits, Gs; D020962:Heterotrimeric GTP-Binding Proteins