Journal
HEART RHYTHM
Volume 6, Issue 12, Pages 1745-1750Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.hrthm.2009.08.031
Keywords
Sudden cardiac arrest; Ventricular tachycardia; Ventricular; fibrillation; Coronary artery disease; Transforming growth factor beta; Genetics
Categories
Funding
- National Center for Research Resources, NIH
- National Institutes of Health Roadmap for Medical Research [KL2 RR024130]
- NATIONAL CENTER FOR RESEARCH RESOURCES [KL2RR024130] Funding Source: NIH RePORTER
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BACKGROUND Transforming growth factor beta (TGF beta) 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 TGF beta pathway genes may be associated with SCA. OBJECTIVE We examined the association of common SNPs among 12 candidate genes in the TGF alpha 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 TGF alpha signaling in SCA susceptibility.
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