RT Journal Article
T1 Genetic Etiology for Alcohol-Induced Cardiac Toxicity.
A1 Ware, James S
A1 Amor-Salamanca, Almudena
A1 Tayal, Upasana
A1 Govind, Risha
A1 Serrano, Isabel
A1 Salazar-Mendiguchia, Joel
A1 Garcia-Pinilla, Jose Manuel
A1 Pascual-Figal, Domingo A
A1 Nuñez, Julio
A1 Guzzo-Merello, Gonzalo
A1 Gonzalez-Vioque, Emiliano
A1 Bardaji, Alfredo
A1 Manito, Nicolas
A1 Lopez-Garrido, Miguel A
A1 Padron-Barthe, Laura
A1 Edwards, Elizabeth
A1 Whiffin, Nicola
A1 Walsh, Roddy
A1 Buchan, Rachel J
A1 Midwinter, William
A1 Wilk, Alicja
A1 Prasad, Sanjay
A1 Pantazis, Antonis
A1 Baski, John
A1 O'Regan, Declan P
A1 Alonso-Pulpon, Luis
A1 Cook, Stuart A
A1 Lara-Pezzi, Enrique
A1 Barton, Paul J
A1 Garcia-Pavia, Pablo
K1 alcohol
K1 dilated cardiomyopathy
K1 genetics
K1 titin
K1 variant
AB 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. 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. 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. 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  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.
PB Elsevier
YR 2018
FD 2018
LK http://hdl.handle.net/10668/12481
UL http://hdl.handle.net/10668/12481
LA en
NO Ware JS, Amor-Salamanca A, Tayal U, Govind R, Serrano I, Salazar-Mendiguchía J. Genetic Etiology for Alcohol-Induced Cardiac Toxicity. J Am Coll Cardiol. 2018 May 22;71(20):2293-2302
DS RISalud
RD Apr 4, 2025