title: Alpha-adducin polymorphism associated with increased risk of adverse cardiovascular outcomes: results from GENEtic Substudy of the INternational VErapamil SR-trandolapril STudy (INVEST-GENES).
abstract: BACKGROUND
  The alpha-adducin (ADD1) Gly460Trp polymorphism has been associated with hypertension and response to diuretic therapy, but controversy exists.
  
  
  METHODS
  The present study was conducted to prospectively investigate the relationship among the ADD1 Gly460Trp polymorphism, diuretic use, and adverse cardiovascular outcomes among 5,979 patients with hypertensive coronary artery disease, who participated in the INVEST and provided genomic DNA. The primary outcome was defined as the first occurrence of nonfatal stroke, nonfatal myocardial infarction, or all-cause death. Secondary outcomes were the components of the primary outcome. Ancestry informative markers were used to control for population stratification.
  
  
  RESULTS
  In blacks, ADD1 variant carriers were at higher risk for a primary outcome event than wild-type homozygotes (adjusted hazard ratio 2.62, 95% CI 1.23-5.58, P = .012), with a similar trend in whites and Hispanics, albeit a smaller magnitude of effect (adjusted hazard ratio 1.43, 0.86-2.39 in Hispanics; 1.24, 0.90-1.71 in whites). Secondary outcome analysis showed that the all-cause death was driving the differences in primary outcomes by genotype. There was no interaction between the ADD1 polymorphism and diuretic use for either primary outcome or secondary outcomes.
  
  
  CONCLUSIONS
  In hypertensive patients with coronary artery disease, black ADD1 variant carriers showed a 2.6-fold excess risk for a primary outcome event and an 8-fold increase risk of death. White and Hispanic ADD1 variant carriers showed an increased but nonsignificant excess risk. However, the effect of diuretic use on risk of cardiovascular outcomes did not vary by ADD1 carrier status.
authors.affiliation: College of Pharmacy, University of Florida, Gainesville, FL 32610-0486, USA.
authors.forename: Tobias
authors.initials: T
authors.lastname: Gerhard
authors.forename: Yan
authors.initials: Y
authors.lastname: Gong
authors.forename: Amber L
authors.initials: AL
authors.lastname: Beitelshees
authors.forename: Xianyun
authors.initials: X
authors.lastname: Mao
authors.forename: Maximilian T
authors.initials: MT
authors.lastname: Lobmeyer
authors.forename: Rhonda M
authors.initials: RM
authors.lastname: Cooper-DeHoff
authors.forename: Taimour Y
authors.initials: TY
authors.lastname: Langaee
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Schork
authors.forename: Mark D
authors.initials: MD
authors.lastname: Shriver
authors.forename: Carl J
authors.initials: CJ
authors.lastname: Pepine
authors.forename: Julie A
authors.initials: JA
authors.lastname: Johnson
mesh_terms: D000368:Aged; D044383:Black People / Q000235:genetics; D002148:Calmodulin-Binding Proteins / Q000235:genetics*; D003324:Coronary Artery Disease / Q000150:complications / Q000208:ethnology / Q000235:genetics*; D003598:Cytoskeletal Proteins / Q000235:genetics*; D004232:Diuretics / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D006630:Hispanic or Latino / Q000235:genetics; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy / Q000208:ethnology / Q000235:genetics*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009026:Mortality; D009203:Myocardial Infarction / Q000453:epidemiology / Q000235:genetics; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D012306:Risk; D020521:Stroke / Q000453:epidemiology / Q000235:genetics; D044465:White People / Q000235:genetics; D000099291:Adducins
chemical_list: D002148:Calmodulin-Binding Proteins; D003598:Cytoskeletal Proteins; D004232:Diuretics; D000099291:Adducins