TY - JOUR
T1 - Association of TGFBR2 polymorphism with risk of sudden cardiac arrest in patients with coronary artery disease
AU - Tseng, Zian H.
AU - Vittinghoff, Eric
AU - Musone, Stacy L.
AU - Lin, Feng
AU - Whiteman, Dean
AU - Pawlikowska, Ludmila
AU - Kwok, Pui Yan
AU - Olgin, Jeffrey E.
AU - Aouizerat, Bradley E.
N1 - Funding Information:
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).
PY - 2009/12
Y1 - 2009/12
N2 - 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.
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.
KW - Coronary artery disease
KW - Genetics
KW - Sudden cardiac arrest
KW - Transforming growth factor ß
KW - Ventricular fibrillation
KW - Ventricular tachycardia
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U2 - 10.1016/j.hrthm.2009.08.031
DO - 10.1016/j.hrthm.2009.08.031
M3 - Article
C2 - 19959123
AN - SCOPUS:70549099836
SN - 1547-5271
VL - 6
SP - 1745
EP - 1750
JO - Heart Rhythm
JF - Heart Rhythm
IS - 12
ER -