β2-Adrenergic Receptor Genotype and Survival Among Patients Receiving β-Blocker Therapy After an Acute Coronary Syndrome

CONTEXT: Previous data support an association between polymorphisms of the beta1- and beta2-adrenergic receptors (ADRB1 and ADRB2) and surrogate end points of response to beta-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 beta-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 beta-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 beta-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 beta-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 beta-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 beta-blocker or no beta-blocker groups. CONCLUSIONS: Patients prescribed beta-blocker therapy after an ACS have differential survival associated with their ADRB2 genotypes. Further assessment of the benefits of beta-blocker therapy in high-risk genotype groups may be warranted.