Association of TGFBR2 polymorphism with risk of sudden cardiac arrest in patients with coronary artery disease

Zian H. Tseng, Eric Vittinghoff, Stacy L. Musone, Feng Lin, Dean Whiteman, Ludmila Pawlikowska, Pui Yan Kwok, Jeffrey E. Olgin, Bradley E. Aouizerat

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1745-1750
Number of pages6
JournalHeart Rhythm
Volume6
Issue number12
DOIs
StatePublished - Dec 2009

Fingerprint

Sudden Cardiac Death
Coronary Artery Disease
Single Nucleotide Polymorphism
Transforming Growth Factors
Cardiac Arrhythmias
Fibrosis
Genes
Case-Control Studies
Healthy Volunteers
Odds Ratio
Confidence Intervals

Keywords

  • Coronary artery disease
  • Genetics
  • Sudden cardiac arrest
  • Transforming growth factor ß
  • Ventricular fibrillation
  • Ventricular tachycardia

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Association of TGFBR2 polymorphism with risk of sudden cardiac arrest in patients with coronary artery disease. / Tseng, Zian H.; Vittinghoff, Eric; Musone, Stacy L.; Lin, Feng; Whiteman, Dean; Pawlikowska, Ludmila; Kwok, Pui Yan; Olgin, Jeffrey E.; Aouizerat, Bradley E.

In: Heart Rhythm, Vol. 6, No. 12, 12.2009, p. 1745-1750.

Research output: Contribution to journalArticle

Tseng, ZH, Vittinghoff, E, Musone, SL, Lin, F, Whiteman, D, Pawlikowska, L, Kwok, PY, Olgin, JE & Aouizerat, BE 2009, 'Association of TGFBR2 polymorphism with risk of sudden cardiac arrest in patients with coronary artery disease', Heart Rhythm, vol. 6, no. 12, pp. 1745-1750. https://doi.org/10.1016/j.hrthm.2009.08.031
Tseng, Zian H. ; Vittinghoff, Eric ; Musone, Stacy L. ; Lin, Feng ; Whiteman, Dean ; Pawlikowska, Ludmila ; Kwok, Pui Yan ; Olgin, Jeffrey E. ; Aouizerat, Bradley E. / Association of TGFBR2 polymorphism with risk of sudden cardiac arrest in patients with coronary artery disease. In: Heart Rhythm. 2009 ; Vol. 6, No. 12. pp. 1745-1750.
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AU - Whiteman, Dean

AU - Pawlikowska, Ludmila

AU - Kwok, Pui Yan

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AU - Aouizerat, Bradley E.

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AB - 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.

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