Gene mutation in some South Asians causes heart failure

A NEW study shows how a genetic defect—found in up to 8% of Indians and other South Asians such as Pakistan and Bangladesh—leads to cardiac dysfunction and potentially fatal heart attacks. 

 

Sakthivel Sadayappan, PhD, MBA, of the Stritch School of Medicine at Loyola University Chicago, led the study published in the Journal of Biological Chemistry of the American Society for Biochemistry and Molecular Biology.

 

The study reports that this gene mutation purportedly impairs the heart’s ability to pump blood, causing hypertrophic cardiomyopathy—the most common form of inherited cardiac disease and the leading cause of sudden cardiac death in young people. 

 

The mutated gene encodes for a protein, called cardiac myosin binding protein-C (cMyBP-C), which controls cardiac muscle contractions and is critical for the normal functioning of the heart. In the mutated gene, 25 base pairs (DNA letters) are missing. As a result, the tail end of the protein is altered.

 

Dr. Sadayappan and colleagues introduced the mutated gene into adult rat cardiomyocytes (heart muscle cells) in a petri dish. These cells were compared with cardiomyocytes that received a normal gene.

 

In cells with the mutant gene, the cMyBP-C protein was not incorporated into sarcomeres, which are the basic units of heart muscle. Rather than helping the sarcomeres contract properly, the mutant protein floated around the cell’s cytoplasm, producing a toxic effect. The study showed, for the first time, that expression of the mutant protein is sufficient to cause cardiac dysfunction.

 

Importantly, the findings point the way toward future treatments that would remove the mutant protein from cells and introduce normal cMyBP-C protein. Researchers also hope to identify lifestyle and environmental risk factors that aggravate hypertrophic cardiomyopathy in people who carry the gene mutation.

 

Carriers of this mutant gene have about an 80% chance of developing heart failure after age 45, according to the report. This is vital information for an estimated 55 million people of South Asian descent worldwide, including 200,000 people in the United States, who carry the potentially fatal mutation.

 

Dr. Sadayappan and his colleagues concluded that determining the disease mechanism will help in developing therapies, and is the “first priority to prevent the development of heart failure in millions of carriers worldwide,” the report stated.