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oai:repisalud.isciii.es:20.500.12105/66692024-11-28T14:56:41Zcom_20.500.12105_19604com_20.500.12105_2051com_20.500.12105_15322col_20.500.12105_19605col_20.500.12105_16927col_20.500.12105_16981col_20.500.12105_16984
Repisalud author Ware, James S. author Amor-Salamanca, Almudena author Tayal, Upasana author Govind, Risha author Serrano, Isabel author Salazar-Mendiguchia, Joel author Manuel Garcia-Pinilla, Jose author Pascual-Figal, Domingo A author Nunez, Julio author Guzzo-Merello, Gonzalo author Gonzalez-Vioque, Emiliano author Bardaji, Alfredo author Manito, Nicolas author Lopez-Garrido, Miguel A. author Padron-Barthe, Laura author Edwards, Elizabeth author Whiffin, Nicola author Walsh, Roddy author Buchan, Rachel J. author Midwinter, William author Wilk, Alicja author Prasad, Sanjay author Pantazis, Antonis author Baski, John author O'Regan, Declan P. author Alonso-Pulpon, Luis author Cook, Stuart A. author Lara-Pezzi, Enrique author Barton, Paul J R author Garcia-Pavia, Pablo funder Instituto de Salud Carlos III funder Ministerio de Economía y Competitividad (España) funder Wellcome Trust funder British Heart Foundation funder Medical Research Council (Reino Unido) funder National Institute for Health Research (Reino Unido) funder Ministerio de Economía, Industria y Competitividad (España) funder Fundación ProCNIC funder Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF) 2018-11-22T08:10:50Z 2018-11-22T08:10:50Z 2018 J Am Coll Cardiol. 2018; 71(20):2293-2302 10.1016/j.jacc.2018.03.462 1558-3597 0735-1097 Journal of the American College of Cardiology http://hdl.handle.net/10668/12481 29773157 http://hdl.handle.net/20.500.12105/6669 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 x10(-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.(C)2018 The Authors. eng Alcohol Dilated cardiomyopathy Genetics Titin Variant DILATED CARDIOMYOPATHY MUTATIONS CONSUMPTION GENOMICS Genetic Etiology for Alcohol-Induced Cardiac Toxicity journal article URL https://repisalud.isciii.es/bitstreams/adf3c04a-902b-4240-86e0-947446a3ffaf/download File MD5 fa96f5243d9db75c38e04b8b1f53f4e6 492974 application/pdf GeneticEtiologyAlcoholInduced_2018.pdf URL https://repisalud.isciii.es/bitstreams/a496dc4a-e797-4a39-943b-34bd60d5124f/download File MD5 ac85f1805bf990d2828882c7fbaa9dad 46240 text/plain GeneticEtiologyAlcoholInduced_2018.pdf.txt