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Title: Genetic Etiology for Alcohol-Induced Cardiac Toxicity
Authors: Ware J.S.
Amor-Salamanca A.
Tayal U.
Govind R.
Serrano I.
Salazar-Mendiguchía J.
García-Pinilla J.M.
Pascual-Figal D.A.
Nuñez J.
Guzzo-Merello G.
Gonzalez-Vioque E.
Bardaji A.
Manito N.
López-Garrido M.A.
Padron-Barthe L.
Edwards E.
Whiffin N.
Walsh R.
Buchan R.J.
Midwinter W.
Wilk A.
Prasad S.
Pantazis A.
Baski J.
O'Regan D.P.
Alonso-Pulpon L.
Cook S.A. 
Lara-Pezzi E.
Barton P.J.
Garcia-Pavia P.
Keywords: alcohol
dilated cardiomyopathy
Issue Date: 2018
Publisher: Elsevier USA
Citation: Ware J.S., Amor-Salamanca A., Tayal U., Govind R., Serrano I., Salazar-Mendiguchía J., García-Pinilla J.M., Pascual-Figal D.A., Nuñez J., Guzzo-Merello G., Gonzalez-Vioque E., Bardaji A., Manito N., López-Garrido M.A., Padron-Barthe L., Edwards E., Whiffin N., Walsh R., Buchan R.J., Midwinter W., Wilk A., Prasad S., Pantazis A., Baski J., O'Regan D.P., Alonso-Pulpon L., Cook S.A., Lara-Pezzi E., Barton P.J., Garcia-Pavia P. (2018). Genetic Etiology for Alcohol-Induced Cardiac Toxicity. Journal of the American College of Cardiology 71 (20) : 2293-2302. ScholarBank@NUS Repository.
Abstract: Background: Alcoholic cardiomyopathy (ACM) is defined by a dilated and impaired left ventricle due to chronic excess alcohol consumption. It is largely unknown which factors determine cardiac toxicity on exposure to alcohol. Objectives: This study sought to evaluate the role of variation in cardiomyopathy-associated genes in the pathophysiology of ACM, and to examine the effects of alcohol intake and genotype on dilated cardiomyopathy (DCM) severity. Methods: The authors characterized 141 ACM cases, 716 DCM cases, and 445 healthy volunteers. The authors compared the prevalence of rare, protein-altering variants in 9 genes associated with inherited DCM. They evaluated the effect of genotype and alcohol consumption on phenotype in DCM. Results: Variants in well-characterized DCM-causing genes were more prevalent in patients with ACM than control subjects (13.5% vs. 2.9%; p = 1.2 ×10?5), but similar between patients with ACM and DCM (19.4%; p = 0.12) and with a predominant burden of titin truncating variants (TTNtv) (9.9%). Separately, we identified an interaction between TTN genotype and excess alcohol consumption in a cohort of DCM patients not meeting ACM criteria. On multivariate analysis, DCM patients with a TTNtv who consumed excess alcohol had an 8.7% absolute reduction in ejection fraction (95% confidence interval: ?2.3% to ?15.1%; p < 0.007) compared with those without TTNtv and excess alcohol consumption. The presence of TTNtv did not predict phenotype, outcome, or functional recovery on treatment in ACM patients. Conclusions: TTNtv represent a prevalent genetic predisposition for ACM, and are also associated with a worse left ventricular ejection fraction in DCM patients who consume alcohol above recommended levels. Familial evaluation and genetic testing should be considered in patients presenting with ACM. © 2018 The Authors
Source Title: Journal of the American College of Cardiology
ISSN: 07351097
DOI: 10.1016/j.jacc.2018.03.462
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