Abstract
BACKGROUND: Previous studies suggest that beta-adrenergic receptor (betaAR) single nucleotide polymorphisms (SNPs) are associated with out-of-hospital sudden cardiac death (SCD) and overall mortality, but did not specifically examine risk of ventricular arrhythmias (VA). OBJECTIVE: This study examined the effects of functional SNPs of beta1AR and beta2AR on the risk of VA and SCD in patients with coronary artery disease (CAD). METHODS: beta1AR (Ser49Gly, Arg389Gly) and beta2AR (Gly16Arg, Gln27Glu) SNPs were genotyped in a case-control study comparing 107 patients with CAD and aborted SCD due to VA with 287 CAD control subjects and 101 healthy control subjects. These variants were also examined in the Heart and Estrogen Replacement Study (HERS) cohort of women with CAD followed for SCD (n = 66) and nonfatal VA (NFVA) (n = 33) over 6.8 years. RESULTS: In the case-control study, no statistically significant association was observed for the odds of SCD with any of the SNPs or haplotypes tested. Similarly, HERS revealed null effects for these SNPs and haplotypes in relation to risk of SCD, SCD + NFVA, and all-cause mortality. Point estimates and confidence intervals for risk of SCD associated with beta2AR27 were similar in both populations (Glu27 carriers vs Gln27 homozygotes: adjusted odds ratio 1.23 [95% confidence interval 0.75 to 2.03, P = .41] in the case-control study, and adjusted relative risk (RR) 1.18 [95% confidence interval 0.69 to 2.00, P = .55] in HERS). These null findings trend in the opposite direction and differ from previous published estimates (P = .01 and .07, respectively). CONCLUSION: We did not find an increase in risk of SCD associated with any of these common betaAR polymorphisms.