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


CONCLUSIONS
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.
Tseng
Zian H
ZH
Section of Cardiac Electrophysiology, Division of Cardiology, Department of Medicine, University of California, San Francisco, California 94143-1354, USA. zhtseng@medicine.ucsf.edu
Vittinghoff
Eric
E
Musone
Stacy L
SL
Lin
Feng
F
Whiteman
Dean
D
Pawlikowska
Ludmila
L
Kwok
Pui-Yan
PY
Olgin
Jeffrey E
JE
Aouizerat
Bradley E
BE
D000368:Aged; D002140:California / Q000453:epidemiology; D016022:Case-Control Studies; D016001:Confidence Intervals; D003324:Coronary Artery Disease / Q000150:complications / Q000453:epidemiology / Q000235:genetics*; D016757:Death, Sudden, Cardiac / Q000453:epidemiology* / Q000209:etiology / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics*; D018570:Risk Assessment; D012307:Risk Factors; D015398:Signal Transduction; D017180:Tachycardia, Ventricular / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha; D014481:United States / Q000453:epidemiology; D014693:Ventricular Fibrillation / Q000453:epidemiology / Q000235:genetics
D018125:Receptors, Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II