Common ß-adrenergic receptor polymorphisms are not associated with risk of sudden cardiac death in patients with coronary artery disease

Zian H. Tseng, Bradley E. Aouizerat, Ludmila Pawlikowska, Eric Vittinghoff, Feng Lin, Dean Whiteman, Annie Poon, David Herrington, Timothy D. Howard, Paul D. Varosy, Stephen B. Hulley, Mary Malloy, John Kane, Pui Yan Kwok, Jeffrey E. Olgin

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)814-821
Number of pages8
JournalHeart Rhythm
Volume5
Issue number6
DOIs
StatePublished - Jun 2008

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Sudden Cardiac Death
Adrenergic Receptors
Coronary Artery Disease
Single Nucleotide Polymorphism
Estrogen Replacement Therapy
Cardiac Arrhythmias
Case-Control Studies
Confidence Intervals
Haplotypes
Mortality
Receptors, Adrenergic, beta
Homozygote
Healthy Volunteers
Cohort Studies
Odds Ratio

Keywords

  • Beta-adrenergic receptors
  • Coronary artery disease
  • Genetics
  • Sudden cardiac death
  • Ventricular arrhythmias

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Medicine(all)

Cite this

Common ß-adrenergic receptor polymorphisms are not associated with risk of sudden cardiac death in patients with coronary artery disease. / Tseng, Zian H.; Aouizerat, Bradley E.; Pawlikowska, Ludmila; Vittinghoff, Eric; Lin, Feng; Whiteman, Dean; Poon, Annie; Herrington, David; Howard, Timothy D.; Varosy, Paul D.; Hulley, Stephen B.; Malloy, Mary; Kane, John; Kwok, Pui Yan; Olgin, Jeffrey E.

In: Heart Rhythm, Vol. 5, No. 6, 06.2008, p. 814-821.

Research output: Contribution to journalArticle

Tseng, ZH, Aouizerat, BE, Pawlikowska, L, Vittinghoff, E, Lin, F, Whiteman, D, Poon, A, Herrington, D, Howard, TD, Varosy, PD, Hulley, SB, Malloy, M, Kane, J, Kwok, PY & Olgin, JE 2008, 'Common ß-adrenergic receptor polymorphisms are not associated with risk of sudden cardiac death in patients with coronary artery disease', Heart Rhythm, vol. 5, no. 6, pp. 814-821. https://doi.org/10.1016/j.hrthm.2008.03.016
Tseng, Zian H. ; Aouizerat, Bradley E. ; Pawlikowska, Ludmila ; Vittinghoff, Eric ; Lin, Feng ; Whiteman, Dean ; Poon, Annie ; Herrington, David ; Howard, Timothy D. ; Varosy, Paul D. ; Hulley, Stephen B. ; Malloy, Mary ; Kane, John ; Kwok, Pui Yan ; Olgin, Jeffrey E. / Common ß-adrenergic receptor polymorphisms are not associated with risk of sudden cardiac death in patients with coronary artery disease. In: Heart Rhythm. 2008 ; Vol. 5, No. 6. pp. 814-821.
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abstract = "Background: Previous studies suggest that beta-adrenergic receptor ({\ss}AR) 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 {\ss}1AR and {\ss}2AR on the risk of VA and SCD in patients with coronary artery disease (CAD). Methods: {\ss}1AR (Ser49Gly, Arg389Gly) and {\ss}2AR (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 {\ss}2AR27 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 {\ss}AR polymorphisms.",
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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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