Researchers evaluate the link between common genetic variant and cardiomyopathy

Researchers found that the majority of study participants with variations in the DNA sequence for the titin gene did not predict signs of cardiac decline or idiopathic dilated cardiomyopathy (DCM)—a potentially life-threatening condition due to enlarged, weakened ventricles that has no known cause.

Titin genetic variants—which are responsible for maintaining the structure of the heart muscle—encode for shortened titin protein variants (TTNtvs). Researchers examined more than 70,000 participants using data available from diagnoses, and test and imaging results to determine the impact of TTNtvs. They identified nearly 500 participants with highly expressed protein-coding regions on the DNA. These variants were linked to an increased risk of dilated cardiomyopathy in people of European ancestry. In reviewing data from the Jackson Heart Study, there was no link between DCM and African ancestry.

The study findings indicate that individuals with TTNtvs may require alternative management strategies for DCM. However, it is also important to note that diseases like DCM may be associated with multiple genes, lifestyle, and environmental factors that could make it difficult to fully understand how TTNtvs impact patients.

“DCM is a complex genetic disease that is likely impacted by the individual’s genetic makeup, how likely the individual is to present with a specific physical trait based on their genetics, and expression patterns of the gene,” said Patrice Desvigne-Nickens, M.D., medical officer of heart failure and arrhythmias at NHLBI.

“While there is no argument regarding the importance of genetic mutations as tools to understand disease mechanisms or progression of complex genetic diseases, additional data demonstrating the clinical utility of the genetic mutation in a seemingly healthy individual is warranted.”

The study, supported by NHLBI, appeared in the journal Circulation, part of the American Heart Association.