title: Pharmacogenetics and healthcare outcomes in patients with chronic heart failure.
abstract: OBJECTIVE
  To test for associations between genetic polymorphisms of adrenergic receptors (AR) and other candidate genes and healthcare utilization in heart failure patients, taking into account other important factors, such as medication adherence.
  
  
  METHODS
  One year-hospital utilization data were collected from 140 participants with heart failure, aged 50 years or older. Medication adherence was measured. Hospitalization and emergency department (ED) visits due to heart failure were used as healthcare outcomes. The genotypes of polymorphisms in six genes were determined: α(2C)-AR (ADRA2C), β₁-AR (ADRB1), β₂-AR (ADRB2), endothelial nitric oxide synthase (eNOS), angiotensin converting enzyme (ACE), and CYP4A11. Haplotypes for ADRB1 and ADRB2 were estimated. The genotype effects on healthcare outcomes were examined using log-linear regression models.
  
  
  RESULTS
  Compared to ADRB1 Arg389 carriers, homozygous Gly389Gly carriers experienced fewer ED visits [incidence rate ratio (IRR) 0.07, 95 % confidence interval (CI) 0.01-0.54, P = 0.022]. Compared to ADRB2 homozygous Gly16Gly carriers, Arg16Gly carriers had fewer ED visits (IRR 0.23, 95 % CI 0.09-0.59, P = 0.006). Polymorphisms in ADRB1 as well as those in ADRB2 were in linkage disequilibrium, with three defining haplotypes, respectively. For ADRB2, the risk of hospitalizations and ED visits were relatively lower in Arg16/Gln27 carriers but relatively higher in homozygous Gly16/Gln27 carriers (P < 0.05). Compared to eNOS 894TT homozygous variants, 894GG and 894GT carriers had notably fewer ED visits (IRR 0.05, 95 % CI 0.01-0.25, P = 0.0013 and IRR 0.10, 95 % CI 0.02-0.42, P = 0.006, respectively). The other polymorphisms showed no association with healthcare outcomes.
  
  
  CONCLUSIONS
  After controlling for demographics, functional status, and treatment adherence, polymorphisms in ADRB1, ADRB2 and eNOS are associated with healthcare outcomes in heart failure patients.
authors.affiliation: Department of Anesthesiology and Pain Medicine, Inje University Sanggye Paik Hospital, 761-1, Sanggye 7-dong, Nowon-gu, Seoul, Korea. kyemin@paik.ac.kr
authors.forename: Kye-Min
authors.initials: KM
authors.lastname: Kim
authors.forename: Michael D
authors.initials: MD
authors.lastname: Murray
authors.forename: Wanzhu
authors.initials: W
authors.lastname: Tu
authors.forename: Jason
authors.initials: J
authors.lastname: Robarge
authors.forename: Yan
authors.initials: Y
authors.lastname: Ding
authors.forename: D Craig
authors.initials: DC
authors.lastname: Brater
authors.forename: David A
authors.initials: DA
authors.lastname: Flockhart
mesh_terms: D000368:Aged; D019943:Amino Acid Substitution; D004636:Emergency Service, Hospital / Q000706:statistics & numerical data; D005260:Female; D005500:Follow-Up Studies; D056726:Genetic Association Studies; D006333:Heart Failure / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000628:therapy*; D006579:Heterozygote; D006760:Hospitalization; D006801:Humans; D007196:Indiana; D008297:Male; D055118:Medication Adherence; D008875:Middle Aged; D052250:Nitric Oxide Synthase Type III / Q000235:genetics* / Q000378:metabolism; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D018342:Receptors, Adrenergic, beta-1 / Q000235:genetics* / Q000378:metabolism; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics* / Q000378:metabolism; D016037:Single-Blind Method
chemical_list: C547787:ADRB1 protein, human; C553443:ADRB2 protein, human; D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III