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Researchers in Bangalore have zeroed in on a gene that may explain why an unusually high number of Indians are prone to coronary artery disease (CAD), the biggest killer among various ailments that afflict the human heart. The risk of CAD is said to be several times higher in Indians than in the others.
CAD is a condition in which plaque builds up inside the coronary artery vessels that supply the heart muscle with oxygen-rich blood.
Led by Arindam Maitra, scientists at the Thrombosis Research Institute — attached to Narayana Hrudayalaya in Bangalore — found that people who harbour a particular variant of the gene rs10757278 are over one and half times more prone to CAD than those who do not have it.
The gene in question is located on the short arm of chromosome 9 (of the 23 pairs that a human cell contains, received from each of the parents). The gene variant was earlier found to put other populations at risk too, but to a much lesser degree.
Maitra, however, was quick to add that this is not the only gene associated with CAD. More genes are suspected to contribute to the inherited risk of CAD. Yet very little is known about them. “This is only the tip of an iceberg,” said Maitra whose team, early last year, unravelled the role played by another gene (IL-6) in the early onset of CAD in Indians.
CAD is multigenic and complex. Being multigenic, no single gene, acting in isolation, will lead to the disease. As a result, people may bear two copies of the risk gene variant but lack the other relevant genetic risk factors which, in combination, might lead to CAD.
And, being complex, CAD is caused by a combination of the presence of the genetic risk factors as well as exposure to risk-conferring environmental influences like diet or lifestyle, said Maitra.
The study, scheduled to appear soon in the Journal of Genetics, looked for the presence of the gene variant in 154 CAD patients undergoing treatment in Bangalore and Mumbai. Similar studies were conducted on an equal number of healthy people.
Patients with two copies of the risk-associated variant — rs10757278G — were found to be far more vulnerable than those with one copy or none at all. Nearly one-third of the patients with three or more diseased artery vessels had two copies of rs10757278G, whereas the frequency was one in eight in the patients who lacked them.
It was also found that CAD sets in two years earlier in those who bear the risk gene variants than those who don’t.
The risk of CAD in Indians is about 3-4 times higher than in the Caucasians, six times higher than in the Chinese and 20 times higher than in the Japanese.
Independent experts, however, dismiss the study because of the small sample size. “Genomic studies are generally conducted with thousands of volunteers, as there is always a chance of getting false positive results otherwise,” said Dorairaj Prabharakan, who heads the non-profit Centre for Chronic Disease Control in New Delhi .
While gene studies may help understand the mechanisms of the disease better, it is quite irrelevant from a clinician’s point of view. Only 10 per cent of CAD could be solely the result of genetic factors, Prabhakaran stressed. The risk factors associated with nearly two-third of CAD patients are smoking and elevated blood fat levels. Another 20 per cent of cases are due to diabetes and hypertension.
Like Prabhakaran, Prashant Joshi, a doctor at the Government Medical College, Nagpur, too feels that the sample size is too low. But, he added, it is very important to know which genes make Indians more vulnerable to CAD. “The threshold of the risk factors in Indians is very low compared with their counterparts in the West,” Joshi said. In other words, Indians with lower cholesterol, diabetes and BP levels, or who smoke less than their counterparts abroad, are more prone to CAD. “Genes are certainly playing a role here,” Joshi said.
Maitra justified the small sample size, saying it was only a pilot study. But, he added, a larger study is already planned.