TY - JOUR
T1 - Common ß-adrenergic receptor polymorphisms are not associated with risk of sudden cardiac death in patients with coronary artery disease
AU - Tseng, Zian H.
AU - Aouizerat, Bradley E.
AU - Pawlikowska, Ludmila
AU - Vittinghoff, Eric
AU - Lin, Feng
AU - Whiteman, Dean
AU - Poon, Annie
AU - Herrington, David
AU - Howard, Timothy D.
AU - Varosy, Paul D.
AU - Hulley, Stephen B.
AU - Malloy, Mary
AU - Kane, John
AU - Kwok, Pui Yan
AU - Olgin, Jeffrey E.
PY - 2008/6
Y1 - 2008/6
N2 - Background: Previous studies suggest that beta-adrenergic receptor (ßAR) 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 ß1AR and ß2AR on the risk of VA and SCD in patients with coronary artery disease (CAD). Methods: ß1AR (Ser49Gly, Arg389Gly) and ß2AR (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 ß2AR27 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 ßAR polymorphisms.
AB - Background: Previous studies suggest that beta-adrenergic receptor (ßAR) 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 ß1AR and ß2AR on the risk of VA and SCD in patients with coronary artery disease (CAD). Methods: ß1AR (Ser49Gly, Arg389Gly) and ß2AR (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 ß2AR27 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 ßAR polymorphisms.
KW - Beta-adrenergic receptors
KW - Coronary artery disease
KW - Genetics
KW - Sudden cardiac death
KW - Ventricular arrhythmias
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U2 - 10.1016/j.hrthm.2008.03.016
DO - 10.1016/j.hrthm.2008.03.016
M3 - Article
C2 - 18534365
AN - SCOPUS:46349106706
SN - 1547-5271
VL - 5
SP - 814
EP - 821
JO - Heart Rhythm
JF - Heart Rhythm
IS - 6
ER -