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.