beta-adrenergic receptor gene polymorphisms and beta-blocker treatment outcomes in hypertension.
Numerous studies have demonstrated that beta(1)- and beta(2)-adrenergic receptor gene (ADRB1 and ADRB2) variants influence cardiovascular risk and beta-blocker responses in hypertension and heart failure. We evaluated the relationship between ADRB1 and ADRB2 haplotypes, cardiovascular risk (death, nonfatal myocardial infarction (MI), and nonfatal stroke), and atenolol-based vs. verapamil sustained-release (SR)-based antihypertensive therapy in 5,895 coronary artery disease (CAD) patients. After an average of 2.8 years, death rates were higher in patients carrying the ADRB1 Ser49-Arg389 haplotype (hazard ratio (HR) 3.66, 95% confidence interval (95% CI) 1.68-7.99). This mortality risk was significant in patients randomly assigned to verapamil SR (HR 8.58, 95% CI 2.06-35.8) but not atenolol (HR 2.31, 95% CI 0.82-6.55), suggesting a protective role for the beta-blocker. ADRB2 haplotype associations were divergent within the treatment groups but did not remain significant after adjustment for multiple comparisons. ADRB1 haplotype variation is associated with mortality risk, and beta-blockers may be preferred in subgroups of patients defined by ADRB1 or ADRB2 polymorphisms.
Pacanowski
M A
MA
Department of Pharmacy Practice and Center for Pharmacogenomics, University of Florida College of Pharmacy, Gainesville, Florida, USA.
Gong
Y
Y
Cooper-Dehoff
R M
RM
Schork
N J
NJ
Shriver
M D
MD
Langaee
T Y
TY
Pepine
C J
CJ
Johnson
J A
JA
D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage*; D000368:Aged; D001262:Atenolol / Q000008:administration & dosage / Q000493:pharmacokinetics; D016001:Confidence Intervals; D003327:Coronary Disease / Q000188:drug therapy / Q000235:genetics / Q000401:mortality; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006579:Heterozygote; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D011336:Probability; D016016:Proportional Hazards Models; D018342:Receptors, Adrenergic, beta-1 / Q000187:drug effects / Q000235:genetics*; D018343:Receptors, Adrenergic, beta-2 / Q000187:drug effects / Q000235:genetics*; D012016:Reference Values; D018570:Risk Assessment; D016019:Survival Analysis; D016896:Treatment Outcome; D014700:Verapamil / Q000008:administration & dosage / Q000493:pharmacokinetics
D000319:Adrenergic beta-Antagonists; D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2; D001262:Atenolol; D014700:Verapamil