Times of India
10 June 2010
Washington, USA

Carries A Gene Mutation That Raises Heart Failure Chances After 45: Study
In India and other south Asian countries, one in 25 people carries a gene mutation that causes heart failure, a new research has found.

Loyola University Health System researcher Sakthivel Sadayappan said that studying this gene and the protein it encodes could lead to new treatments for heart failure. He has studied the gene and protein for 15 years. Investigating the protein could provide ‘a better understanding of the mechanics of heart function during health and disease,’ Sadayappan and first author David Barefield said.

Previous studies by Sadayappan and other researchers found that about 4% of people who live in India, Pakistan, Sri Lanka, Indonesia and Malaysia carry the mutation. Carriers have about a 90% chance of developing heart failure after age 45.

About 60 million people worldwide, including about 40 million Indians, carry the mutation.

Sadayappan said the mutation likely arose in a single person roughly 33,000 years ago, and spread throughout south Asia. The gene encodes for a protein, called cardiac myosin binding protein-C (cMyBP-C), that is critical for 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.

Due to this modification, the protein is not properly incorporated into the functioning unit of cardiac muscle called sarcomere. Consequently, the heart does not contract properly.

In young carriers, the heart can compensate for this defect. But as the person ages, the heart is no longer able to compensate. Heart muscle becomes inflamed and does not work well, a condition called cardiomyopathy.

The most common manifestation of cardiomyopathy is heart failure—the heart can’t pump enough blood to the rest of the body. There is no current treatment to prevent heart failure in people who carry the mutated gene. However, a heart-healthy diet and exercise can delay onset of heart failure, and heart failure drugs can manage symptoms.

Sadayappan said stem cell therapy could be a possible treatment. Stem cells would be taken from a patient’s heart, genetically engineered to replace the mutated gene with a healthy gene, and then injected back in the patient’s heart. But such therapy has not been tested. Nor is there a commercial test for the gene. But Sadayappan and others are actively researching how cMyBP-C functions. And improved understanding of this crucial protein could lead to new drugs to treat heart failure.

The study has been published in the Journal of Molecular and Cellular Cardiology.

The gene encodes for a protein that’s critical for normal heart functioning

In the mutated gene, 25 DNA letters are missing. Consequently, the heart does not contract properly

As the person ages, heart muscles cannot pump enough blood