An estimated 60 million people, virtually all of them on the Indian subcontinent, carry a mutated gene that makes them all but certain to develop heart disease in their 40s and 50s and to suffer an early death, researchers are reporting today.
Though heart disease is the leading cause of death around the world, it is an even more serious problem in India. By next year, according to Indian scientists, the country will carry 60% of the world's burden of heart disease, and this defective gene may be the major reason why.
The gene is a mutant form of the gene that codes for a protein called cardiac myosin binding protein C, or MYBPC3, that is missing a 25-base-pair segment. It was discovered five years ago in two families with a high incidence of cardiomyopathy, in which the heart muscle becomes inflamed and doesn't work as well as it should.
Biochemist Perundurai S. Dhandapany of Madurai Kamaraj University in Madurai, India, and his colleagues initially studied 800 cardiac patients in nine cities in India and compared them to 699 carefully matched controls. They report today in the journal Nature Genetics that patients carrying one copy of the mutant gene are a staggering seven times more likely to develop heart disease than those without it, making them nearly certain to develop the disease.
Patients with the mutant gene appear healthy throughout the early part of their lives, but the abnormal protein manufactured from the gene slowly accumulates. After they turn 45 or so, the abundance of the abnormal protein triggers cardiomyopathy or other symptoms.
The team found only three people who had two copies of the abnormal gene. Two of them developed severe heart disease before the age of 3.
Next, the researchers screened 6,273 randomly selected individuals from 107 ethnic populations in India and found that in all of the groups -- including Hindus, Sikhs, Muslims and Christians -- a uniform 4% had the defect. The incidence was significantly higher in the western and southern states than in the northern states, however -- regions that have the highest incidence of heart disease in the country.
Finally, the researchers screened an additional 2,085 individuals from 70 ethnic groups in 26 other countries, including the United States. They found that the genetic defect is present only in India, Pakistan, Sri Lanka, Indonesia and Malaysia. They estimate that about 60 million people carry it.
Genetic analysis suggests that the mutation arose by chance in India about 33,000 years ago, after modern humans had immigrated to the Indian subcontinent from Africa. It then spread slowly to nearby countries, but remained largely restricted to the region.
It is unusual for such a deleterious genetic effect to persist in a population, noted co-author Chris Tyler-Smith of the Wellcome Trust Sanger Institute in Hinxton, U.K. But in this case, he noted, the gene does its dirty work after the carrier has passed through his or her reproductive years. "It's been able to spread because its effects usually develop only after people have had their children," he noted. It's "a case of chance genetic drift: simply terribly bad luck for the carriers."
Physicians should soon be able to screen for the mutation in parents and their offspring, Dhandapany said. When it is present, victims can be counseled to minimize their other cardiovascular risks to increase their chances of a longer life.
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