Heart Rhythm
Volume 5, Issue 6 , Pages 814-821, June 2008

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

  • Zian H. Tseng, MD, MAS

      Affiliations

    • Section of Cardiac Electrophysiology, Division of Cardiology, Department of Medicine, University of California, San Francisco
    • Corresponding Author InformationAddress reprint requests and correspondence: Dr. Zian H. Tseng, Section of Cardiac Electrophysiology, 500 Parnassus Avenue, Box 1354, University of California, San Francisco, San Francisco, California 94143-1354.
    • ,
  • Bradley E. Aouizerat, PhD

      Affiliations

    • Department of Physiologic Nursing, University of California, San Francisco
    • Institute for Human Genetics, University of California, San Francisco
    • ,
  • Ludmila Pawlikowska, PhD

      Affiliations

    • Institute for Human Genetics, University of California, San Francisco
    • ,
  • Eric Vittinghoff, PhD, MPH

      Affiliations

    • Department of Epidemiology and Biostatistics, University of California, San Francisco
    • ,
  • Feng Lin, MS

      Affiliations

    • Department of Epidemiology and Biostatistics, University of California, San Francisco
    • ,
  • Dean Whiteman, BS

      Affiliations

    • Section of Cardiac Electrophysiology, Division of Cardiology, Department of Medicine, University of California, San Francisco
    • ,
  • Annie Poon, BA

      Affiliations

    • Institute for Human Genetics, University of California, San Francisco
    • ,
  • David Herrington, MD, MHS

      Affiliations

    • Department of Internal Medicine, Wake Forest University, Winston-Salem, North Carolina
    • ,
  • Timothy D. Howard, PhD

      Affiliations

    • Department of Pediatrics, Wake Forest University, Winston-Salem, North Carolina
    • ,
  • Paul D. Varosy, MD

      Affiliations

    • Division of Cardiology, Department of Medicine, Veterans Affairs Medical Center, University of California, San Francisco
    • ,
  • Stephen B. Hulley, MD, MPH

      Affiliations

    • Department of Epidemiology and Biostatistics, University of California, San Francisco
    • ,
  • Mary Malloy, MD

      Affiliations

    • Cardiovascular Research Institute, University of California, San Francisco.
    • ,
  • John Kane, MD, PhD

      Affiliations

    • Cardiovascular Research Institute, University of California, San Francisco.
    • ,
  • Pui-Yan Kwok, MD, PhD

      Affiliations

    • Institute for Human Genetics, University of California, San Francisco
    • Cardiovascular Research Institute, University of California, San Francisco.
    • ,
  • Jeffrey E. Olgin, MD, FHRS

      Affiliations

    • Section of Cardiac Electrophysiology, Division of Cardiology, Department of Medicine, University of California, San Francisco

Received 8 December 2007; accepted 11 March 2008. published online 17 March 2008.

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.

Keywords: Sudden cardiac death, Ventricular arrhythmias, Genetics, Beta-adrenergic receptors, Coronary artery disease

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 This research was funded by grants from the National Center for Research Resources, a component of the National Institutes of Health and the National Institutes of Health Roadmap for Medical Research (KL2 RR024130).

 The authors thank Mintu Turakhia, MD, and Clive Pullinger, PhD, for assistance with the UCSF SCD Study, Jon Witte, PhD, for critical evaluation of the manuscript and Kimberly Lee, MD, for assistance with the figures.

PII: S1547-5271(08)00280-4

doi:10.1016/j.hrthm.2008.03.016

Heart Rhythm
Volume 5, Issue 6 , Pages 814-821, June 2008

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