A mutation in one of the major genes involved in maintaining the structure of cardiac muscle and regulated cardiac condition in Indians may accelerate the number of cardiac patients in India, according to a study conducted by a team of scientists lead by the Hyderabad-based Centre for Cellular and Molecular Biology (CCMB).

An international team of 25 researchers led by CCMB scientists published their study in the scientific journal Nature Genetics from the United States of America. The study reveals that mutations in Myosin binding protein-C (MYBPC3), one of the major genes involved in maintaining the structure of cardiac muscle which regulates cardiac contraction, accounts for about 44 per cent of the sudden cardiac arrest.

Scientists have analysed the DNA (genetic material) of 800 cardiac patients - who were reporting to cardiac centres at Hyderabad, Madurai, Thirunalveli, Tiruvananthapuram, Kozhikode, Mumbai, Bhubaneswar, Delhi and Chandigargh - along with age and ethnically matched 699 normal individuals.

The scientists found that a 25 base pair deletion within the gene making the heart protein MYBPC was significantly more frequent in cardiac patients compared to the normal individuals. In addition, they found that if an individual had both copies of this gene defective (homozygous, containing the 25 base pair deletion), the person may die at a very early age before reaching 5 years. They confirmed this by analysing post-mortem samples with a history of sudden cardiac arrest. But, if the individuals carry the mutation in only one copy of the gene (heterozygous), they can live without any symptoms of heart problems up to the age of 45; however, beyond 45 years they suffer from a range of effects, including sudden heart attack leading to death.

Since the deletion leads to the formation of an abnormal protein, such individuals, therefore, have both abnormal as well as normal proteins. In young people this abnormal protein is degraded efficiently by cellular machinery called the proteasome and carriers thus remain healthy, but as they get older the protein degrading machinery becomes inefficient and leads to a build-up of abnormal protein eventually resulting in symptoms of cardiac problem and leading to sudden heart attack.

It is estimated that the highest death rates in India are associated with problems of the heart and blood circulatory system in people aged 35-64 years. According to a conservative estimate, at least 30 million people suffer from heart diseases in India. By the year 2010, India will carry 60 per cent of the burden of world's heart diseases.


Scientists also conducted screening on 6273 randomly selected individuals from 107 ethnic populations, including primitive tribes, tribes, castes and sub-castes belonging to all religious groups living across India, and found that about 4 per cent of the individuals studied had this genetic defect (25 base pair deletion in the gene MYBPC3).

Scientists investigated whether this genetic abnormality is restricted to India or is widely distributed all over the world. They analysed the DNA of an additional 2085 individuals belonging to 70 populations from 26 countries and found that this genetic defect is present only in the people of the Indian subcontinent and nearby including India, Pakistan, Sri Lanka, Indonesia and Malaysia, but not in other countries.