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(Circulation. 2006;113:1842-1848.)
© 2006 American Heart Association, Inc.

Epidemiology

ß2-Adrenergic Receptor Genetic Variants and Risk of Sudden Cardiac Death

Nona Sotoodehnia, MD, MPH; David S. Siscovick, MD, MPH; Matteo Vatta, PhD; Bruce M. Psaty, MD, PhD; Russell P. Tracy, PhD; Jeffrey A. Towbin, MD, MS; Rozenn N. Lemaitre, PhD, MPH; Thomas D. Rea, MD, MPH; J. Peter Durda, BS; Joel M. Chang, BS; Thomas S. Lumley, PhD; Lewis H. Kuller, MD, PhD; Gregory L. Burke, MD, MSc; Susan R. Heckbert, MD, PhD

From the Cardiovascular Health Research Unit, Department of Medicine (N.S., D.S.S., B.M.P., R.N.L., T.D.R., T.S.L., S.R.H.), Division of Cardiology, Department of Medicine (N.S.), Department of Epidemiology (D.S.S., B.M.P., S.R.H.), and Department of Biostatistics (T.S.L.), University of Washington, Seattle; Department of Pediatrics, Baylor College of Medicine, Houston, Tex (M.V., J.A.T., J.M.C.); Department of Pathology, University of Vermont, Burlington (R.P.T., J.P.D.) Department of Epidemiology, University of Pittsburgh, Pittsburgh, Pa (L.H.K.); and Department of Public Health Sciences, Wake Forest University, Winston-Salem, NC (G.L.B.).

Correspondence to Nona Sotoodehnia, MD, MPH, Cardiovascular Health Research Unit, 1730 Minor Ave, Suite 1360, UW Box 358085, Seattle, WA 98101. E-mail nsotoo{at}u.washington.edu

Received August 11, 2005; revision received January 12, 2006; accepted January 23, 2006.

Background— Sympathetic activation influences the risk of ventricular arrhythmias and sudden cardiac death (SCD), mediated in part by the ß2-adrenergic receptor (B2AR). We investigated whether variation in the B2AR gene is associated with SCD risk.

Methods and Results— In this study, 4441 white and 808 black Cardiovascular Health Study (CHS) participants were followed up prospectively for SCD and genotyped for B2AR Gly16Arg and Gln27Glu polymorphisms. The study was replicated in 155 case and 144 control white subjects in a population-based case-control study of SCD, the Cardiac Arrest Blood Study (CABS). In CHS, Gly16 and Gln27 allele frequencies were 62.4% and 57.1% among white and 50.1% and 81.4% among black participants. Over a median follow-up of 11.1 years, 156 and 39 SCD events occurred in white and black participants, respectively. The Gln27Glu variant was associated with SCD risk (P=0.008 for general model). SCD risk was higher in Gln27 homozygous participants than in Glu27 carriers (ethnicity-adjusted hazard ratio [HR], 1.56; 95% confidence interval [CI], 1.17 to 2.09; P=0.003). The increased risk did not differ significantly between white (HR, 1.62; 95% CI, 1.18 to 2.23) and black (HR, 1.23; 95% CI, 0.61 to 2.48) participants, although the confidence interval was wide in blacks. In the CABS replication study, Gln27 homozygous participants similarly had higher SCD risk than Glu27 carriers (odds ratio, 1.64; 95% CI, 1.02 to 2.63; P=0.040). Gly16Arg was not associated with SCD risk in either study.

Conclusions— Gln27 homozygous individuals have an increased risk of SCD in 2 study populations. Our findings suggest that B2AR plays a role in SCD in humans. Study of genetic variation within the B2AR gene may help identify those at increased SCD risk.

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