Genetic variant may contribute to alcoholic cardiomyopathy

Researchers have identified a genetic variant that may predispose individuals to alcoholic cardiomyopathy (ACM), possibly opening the door for genetic testing and familial evaluation.

Lead author James S. Ware, PhD, with Imperial College London, and colleagues studied the prevalence of protein-altering variants in nine genes among 141 patients with ACM, 716 with dilated cardiomyopathy (DCM) and 445 healthy volunteers. They found titin truncating variants (TTNtv) accounted for 9.9 percent of the 13.5 percent of genetic variants among individuals with ACM. In contrast, only 2.9 percent of healthy individuals showed any genetic variations.

People with DCM were found to have a similar prevalence of overall genetic variants and TTNtv as those with ACM, and excessive alcohol consumption in combination with TTNtv was found to reduce left ventricular ejection fraction (LVEF) by an average of 8.7 percent among those with DCM.

“Variants in DCM-associated genes are more frequent in patients with ACM than in the general population, and patients with DCM and TTNtv who drink alcohol excessively are more prone to decline in LVEF than those who drink less or lack these genetic variants,” Ware and colleagues concluded in the Journal of the American College of Cardiology.

Although it isn’t possible to determine causality at this point, the authors said the evidence points to TTNtv and excessive alcohol consumption being a double whammy that contributes to alcoholic cardiomyopathy.

“The positive cardiac response on reduction or cessation of alcohol points to an etiological role of alcohol in the disease process, and the observed synergistic interaction between genetic predisposition and environmental toxin in the DCM cohort once again points to a biological interaction,” they wrote.

That said, Ware and coauthors acknowledged much is still unknown about the molecular mechanisms for ACM and how they may interact with alcohol exposure. In the study, ACM subjects self-reported consuming about six standard U.S. drinks per day.

“In some families with DCM, TTNtv appear highly penetrant and sufficient to cause disease in isolation, but TTNtv are also seen in approximately 1 percent of the general population, a level well above the prevalence of DCM and suggesting that other genetic or environmental factors contribute to the cardiomyopathic process,” Ware et al. noted.

The study only analyzed specific genes previously linked to DCM, and patients’ self-reported alcohol consumption may have been inaccurate or underreported, the researchers acknowledged. It was also missing another group that could have been informative for comparison: individuals with an excessive drinking history but no cardiomyopathy.

“In individuals presenting with ACM, it seems appropriate to obtain familial evaluation and a three-generation pedigree analysis, to determine whether there is a family history of ACM for ≥3 generations, and to consider genetic testing,” wrote Mariann R. Piano, PhD, with Vanderbilt University School of Nursing, in an accompanying editorial.