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Scientists have found that a mutated gene involved in making cardiac muscles is responsible for the prevalence of cardiac diseases in India.
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Scientists have exposed a chink in the genetic armour of Indians — an inherited handicap that puts 60 million people in the Indian sub-continent at the risk of heart failure.
The genetic vulnerability to heart diseases, unearthed by a team of Indian researchers, comes in the form of a mutation in one of the seven genes that make the human heart muscles and may, partly, explain the higher incidence of heart diseases among Indians. The mutation is on account of a minor deletion in the gene.
The landmark study, which appeared yesterday in the journal Nature Genetics, found that the defective gene exacerbates by seven times its carrier’s risk of suffering from cardiomyopathy, a frequent cause of death. The defective gene has been circulating only in the people of South Asian origin for the last 33,000 years and puts nearly 4 per cent of the current population at risk.
So far, scientists elsewhere have identified 20 genes associated with cardiac disease. “This is the first ever major gene in the Indian population that has been implicated in heart complications,” says Kumarasamy Thangaraj, lead author of the study and a researcher at the Centre for Cellular and Molecular Biology, Hyderabad.
This genetic mutation is also present in certain ethnic communities of Pakistan, Sri Lanka, Indonesia and Malaysia, all said to be Indian ancestry. Sri Lankans and the Burusho community from northern Pakistan have the highest prevalence of the genetic defect — nine out of every 100 people. This is more than double the average prevalence in India.
Within the country, the mutation is higher than the national average in several states. Bihar tops the list with 8 per cent, followed by Orissa (7 per cent) Kerala and Kashmir (6 per cent each). Significantly, the mutation is absent in the Andaman and Nicobar Islands and the northeastern states.
This isn’t surprising as anthropological evidence to shows that ancestors of these people reached India in another wave of migration precededing the journey of the forefathers of those who people the rest of the country, points out Thangaraj.
Conservative estimates show that nearly 30 million Indians suffer from heart diseases, and it is feared that by 2010 India will carry 60 per cent of the world’s heart disease burden. India is projected to lose nearly 18 million man-years by 2030 (10 times more than the US) due to heart failures.
Perundurai Dhandapany, the first author and a researcher at Madurai Kamaraj University, Tamil Nadu, and Thangaraj commenced the study by analysing the genetic material (DNA) of 800 cardiac patients in cities across the country, including Hyderabad, Madurai, Thiruvananthapuram and Delhi. Subsequently, they screened nearly 6,300 people of 107 ethnic communities across three major religions to see how widespread the mutation is.
The gene in question makes myosin binding protein-C (MYBPC3), critical for maintaining the structure of cardiac muscles. It is essential for regulating cardiac contraction. The genetic defect deadly as it is found to be involved in all three different types of cardiomyopathies with distinctly different symptoms.
The most common one is known as dilative cardiomyopathy and is precipitated by stretched heart muscles that make the heart too weak to pump normally. The second one, called hypertrophic cardiomyopathy, is caused by enlargement of muscle mass in the one of the ventricles. The third, restrictive cardiomyopathy — as the name suggests — is caused by rigid heart muscles.
Cardiomyopathies are dangerous, being the leading cause of sudden cardiac deaths, says Dhandapany. It has been found to be the underlying cause in many sports personalities who have died while playing. It is said that one in every 50 Indians and one in every 250 Indians are susceptible, respectively, to dilative and hypertrophic cardiomyopathies, he says. A prominent personality who died of cardiomypathy complications is former union minister Murasoli Maran.
The researchers say that persons with two copies of the defective gene (received one each from each parent) may be at a higher risk and may even die at a young age. Individuals with the mutation in only one copy can live without symptoms of heart problems up to the age of 45. Beyond that, symptoms may catch up, even leading to death due to a subsequent heart attack.
Since the deletion in the gene leads to the formation of an abnormal protein, such individuals have both abnormal as well as normal proteins. In young people this abnormal protein is degraded efficiently by a cellular machinery called proteasome, and carriers thus remain healthy. But as they get older the machinery becomes inefficient and leads to a build up of abnormal protein, eventually resulting in symptoms of cardiac problems and leading to a sudden heart attack, say the researchers.
Prashant Joshi, professor of medicine at Indira Gandhi Medical College, Nagpur, says the study is commendable as it has been able to locate a genetic mutation so widespread. “Understanding one’s genetic vulnerability to heart diseases always helps as he or she can be told to reduce additional risk factors precipitated by sedentary lifestyle, smoking and alcohol,” says Joshi.
Dhandapany, currently at Mount Sinai Medical Center in New York, says that the origin of the genetic mutation could be traced to Maharashtra as more samples from there were found to be carrying two copies of the defective gene.
Sources: The Telegraph (Kolkata, India)
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