Heart Rhythm
Volume 6, Issue 12 , Pages 1745-1750, December 2009

Association of TGFBR2 polymorphism with risk of sudden cardiac arrest 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, California
    • 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
    • ,
  • Eric Vittinghoff, PhD, MPH

      Affiliations

    • Department of Epidemiology and Biostatistics, University of California, San Francisco, California
    • ,
  • Stacy L. Musone, BA

      Affiliations

    • Institute for Human Genetics, University of California, San Francisco, California
    • ,
  • Feng Lin, MS

      Affiliations

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

      Affiliations

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

      Affiliations

    • Institute for Human Genetics, University of California, San Francisco, California
    • Department of Anesthesia and Perioperative Care, University of California, San Francisco, California
    • ,
  • Pui-Yan Kwok, MD, PhD

      Affiliations

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

      Affiliations

    • Section of Cardiac Electrophysiology, Division of Cardiology, Department of Medicine, University of California, San Francisco, California
    • Cardiovascular Research Institute, University of California, San Francisco, California
    • ,
  • Bradley E. Aouizerat, PhD, MAS

      Affiliations

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

Received 30 July 2009; accepted 23 August 2009. published online 01 September 2009.

Background

Transforming growth factor ß (TGFß) signaling has been shown to promote myocardial fibrosis and remodeling with coronary artery disease (CAD), and previous studies show a major role for fibrosis in the initiation of malignant ventricular arrhythmias (VA) and sudden cardiac arrest (SCA). Common single nucleotide polymorphisms (SNPs) in TGFß pathway genes may be associated with SCA.

Objective

We examined the association of common SNPs among 12 candidate genes in the TGFß pathway with the risk of SCA.

Methods

SNPs (n = 617) were genotyped in a case-control study comparing 89 patients with CAD and SCA caused by VA to 520 healthy control subjects.

Results

Nineteen SNPs among 5 genes (TGFB2, TGFBR2, SMAD1, SMAD3, SMAD6) were associated with SCA after adjustment for age and sex. After permutation analysis to account for multiple testing, a single SNP in TGFBR2 (rs9838682) was associated with SCA (odds ratio: 1.66, 95% confidence interval: 1.08 to 2.54, P = .02).

Conclusion

We show an association between a common TGFBR2 polymorphism and risk of SCA caused by VA in the setting of CAD. If validated, these findings support the role of genetic variation in TGFß signaling in SCA susceptibility.

Keywords: Sudden cardiac arrest, Ventricular tachycardia, Ventricular fibrillation, Coronary artery disease, Transforming growth factor ß, Genetics

Abbreviations: CAD, coronary artery disease, CI, confidence interval, LD, linkage disequilibrium, MI, myocardial infarction, OR, odds ratio, PCA, principal component analysis, SCA, sudden cardiac arrest, SCD, sudden cardiac death, SNP, single nucleotide polymorphism, TGF, transforming growth factor, VA, ventricular arrhythmia, VF, ventricular fibrillation, VT, ventricular tachycardia

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 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).

PII: S1547-5271(09)00935-7

doi:10.1016/j.hrthm.2009.08.031

Heart Rhythm
Volume 6, Issue 12 , Pages 1745-1750, December 2009

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