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Heart disease gene variant widespread in South Asians

Thiruvananthapuram: Some four per cent of Indians are carrying a gene variant that greatly increases their propensity to develop cardiomyopathy, a condition affecting heart muscles that often leads to heart failure, according to research carried out by an international team of 25 scientists from four countries.

The variant involves a deletion of 25 “letters” in the genetic code for the MYBPC3 gene that allows cells to produce cardiac myosin binding protein C. The protein is vital for the proper structural organisation of heart muscles.

The mutation in the gene appears to have arisen around 33,000 years ago in India and spread to Pakistan, Sri Lanka, Malaysia and Indonesia, said Kumarasamy Thangaraj of the Centre for Cellular and Molecular Biology in Hyderabad. He led the study that is being published online in the journal Nature Genetics.

Those carrying the defective form of the gene have about a seven fold greater risk of developing cardiomyopathy, observed Perundurai S. Dhandapany, the paper’s first author, who is currently at the Mount Sinai School of Medicine in New York. This is a high level of risk for a commonly occurring gene variant, he told The Hindu.

After screening over 6,000 individuals belonging to 107 ethnic populations in States across the country, the scientists found that the mutated version of the gene was present in all major Indian populations at frequencies ranging from two per cent to eight per cent.

The mutation was present in significantly higher frequencies in southern and western States compared to northern States. People from the north-eastern States as well as the Andaman islands seem to be free of the mutation.

This difference in the gene frequency could be contributing to heart failure being more prevalent in the south of the country than in the north and north-east, the scientists noted. (Heart failure occurs when the heart is for any reason unable to pump sufficient quantities of blood.)

The scientists studied the frequency of the deletion in the MYBPC3 gene among 800 cardiomyopathy patients who came to cardiac centres in Madurai, Tirunelveli, Thiruvananthapuram, Kozhikode, Hyderabad, Mumbai, Bhubaneswar, Delhi and Chandigarh. This was then compared to the frequency of the deletion in 699 normal individuals who matched the patients in age, sex, geographic location and ethnicity.

Nearly 11 per cent of the cardiomyopathy patients had the gene deletion while it was present in less than 2 per cent of the normal individuals.

The scientists also assessed 28 unrelated families with a total of 120 members. These families were chosen because one or more of their members had some form of cardiomyopathy and carried the gene deletion.

Individuals who inherited the shortened version of the gene from only one parent could often live without any symptoms of heart problems till their mid-forties, according to Dr. Thangaraj. But thereafter such individuals could suffer a range of effects, including sudden heart attack leading to death. Those with the mutation in both copies of the gene might be at greater risk.

In young people carrying the gene deletion, it could be that their cellular machinery was able to efficiently remove the abnormal protein produced by the gene, he suggested. So these people remained healthy. But as they got older, the protein degradation mechanism in their cells became inefficient. As a result, levels of the abnormal protein built up in their heart muscles, which eventually resulted in cardiac problems.

The gene variant has persisted in South Asian populations because it affects people only after they have had children, he pointed out.

Identification of the gene variant could not be used as a clinical tool by doctors in treating patients, remarked Jagan Mohan Tharkan, head of cardiology at the Sree Chitra Tirunal Institute of Medical Sciences and Technology in Thiruvananthapuram, and one of the authors of the paper.

At present, it is useful as an investigative tool to understand the disease process, he added.

The paper, however, notes that “genotyping could be used for the identification of persons at risk of heart failure among South Asians and could be accompanied by advice for a lower-risk lifestyle.”

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