2024-03-29T12:36:20Zhttp://repisalud.isciii.es/oai/requestoai:repisalud.isciii.es:20.500.12105/66692024-01-29T20:55:24Zcom_20.500.12105_15322com_20.500.12105_2051com_20.500.12105_2145com_20.500.12105_2144col_20.500.12105_16984col_20.500.12105_16981col_20.500.12105_16927col_20.500.12105_2146
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
0735-1097
http://hdl.handle.net/10668/12481
http://hdl.handle.net/20.500.12105/6669
29773157
10.1016/j.jacc.2018.03.462
1558-3597
Journal of the American College of Cardiology
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/bitstream/20.500.12105/6669/1/GeneticEtiologyAlcoholInduced_2018.pdf
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GeneticEtiologyAlcoholInduced_2018.pdf
URL
https://repisalud.isciii.es/bitstream/20.500.12105/6669/4/GeneticEtiologyAlcoholInduced_2018.pdf.txt
File
MD5
ac85f1805bf990d2828882c7fbaa9dad
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text/plain
GeneticEtiologyAlcoholInduced_2018.pdf.txt