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 2-Adrenergic Receptor Genotype and Survival Among Patients Receiving -Blocker Therapy After an Acute Coronary Syndrome
David E. Lanfear, MD;
Philip G. Jones, MS;
Sharon Marsh, PhD;
Sharon Cresci, MD;
Howard L. McLeod, PharmD;
John A. Spertus, MD, MPH
JAMA. 2005;294:1526-1533.
Context Previous data support an association between polymorphisms of the  1- and 2-adrenergic receptors (ADRB1 and ADRB2) and surrogate end points of response to -adrenergic blocker therapy. However, no associations between these polymorphisms and mortality have been demonstrated.
Objective To evaluate the effect of ADRB1 Arg389Gly (1165 CG), Ser49Gly (145 AG), and ADRB2 Gly16Arg (46 GA), Gln27Glu (79 CG) genotypes on survival among patients discharged with prescribed -blockers after an acute coronary syndrome (ACS).
Design, Setting, and Patients Prospective cohort study of 735 ACS patients admitted to 2 Kansas City, Mo, medical centers between March 2001 and October 2002; 597 patients were discharged with -blocker therapy.
Main Outcome Measure Multivariable-adjusted time to all-cause 3-year mortality.
Results There were 84 deaths during follow-up. There was a significant association between ADRB2 genotype and 3-year mortality among patients prescribed -blocker therapy. For the 79 CG polymorphism, Kaplan-Meier 3-year mortality rates were 16% (35 deaths), 11% (27 deaths), and 6% (4 deaths) for the CC, CG, and GG genotypes, respectively (P = .03; adjusted hazard ratios [AHRs], 0.51 [95% confidence interval {CI}, 0.30-0.87] for CG vs CC and 0.24 (95% CI, 0.09-0.68) for GG vs CC, P = .004). For the ADRB2 46 GA polymorphism, 3-year Kaplan-Meier mortality estimates were 10% (17 deaths), 10% (28 deaths), and 20% (20 deaths) for the GG, GA, and AA genotypes, respectively (P = .005; AHRs, 0.48 [95% CI, 0.27-0.86] for GA vs AA and 0.44 [95% CI, 0.22-0.85] for GG vs AA, P = .02). No mortality difference between genotypes was found among patients not discharged with -blocker therapy for either the 79 CG or 46 GA polymorphisms (P = .98 and P = .49, respectively). The ADRB2 diplotype and compound genotypes were predictive of survival in patients treated with -blockers (P = .04 and P = .002; AHRs, 5.36 [95% CI, 1.83-15.69] and 2.41 [95% CI, 0.86-6.74] for 46 A homozygous and composite heterozygous vs 79 G homozygous, respectively). No association of the ADRB1 variants with mortality was observed in either the -blocker or no -blocker groups.
Conclusions Patients prescribed -blocker therapy after an ACS have differential survival associated with their ADRB2 genotypes. Further assessment of the benefits of -blocker therapy in high-risk genotype groups may be warranted.
Author Affiliations: Departments of Medicine (Drs Lanfear, Marsh, Cresci, and McLeod), Genetics (Dr McLeod), and Molecular Biology and Pharmacology (Dr McLeod), Washington University School of Medicine, St Louis, Mo; Mid America Heart Institute, St Luke’s Hospital, Kansas City, Mo (Mr Jones and Dr Spertus); and the Department of Medicine, University of Missouri, Kansas City (Dr Spertus). Dr Lanfear is now with the Department of Medicine, Henry Ford Hospital, Detroit, Mich.
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