Scientists unravel new diabetes gene

New Delhi, Nov. 12: Scientists have identified a novel candidate gene for diabetes that they say appears to put Indians at a higher risk of the disease than any of the 56 diabetes genes discovered earlier.

A consortium of Indian researchers announced today that the new gene also seems to establish a link between the brain and diabetes, hinting at previously unknown disease mechanisms that scientists hope will eventually lead to new treatment strategies.

The gene called TMEM163, identified by the Indian Diabetes Consortium, makes a protein that plays a role in the transfer of signals between brain cells. Most of the earlier diabetes genes influence either the behaviour of insulin-producing cells in the pancreas or mechanisms of insulin resistance.

"We now have a new hypothesis about diabetes," said Dwaipayan Bharadwaj, a scientist at the Institute of Genomics and Integrative Biology in New Delhi and a member of the consortium. "People with one version of this gene are at risk of developing defective insulin secretion ' we're now trying to validate this idea through laboratory and animal experiments."

Bharadwaj and his colleagues identified the gene through India's largest genome study for diabetes that looked for genetic differences between 6700 patients with diabetes and 5700 persons without the disease. Their findings are scheduled for publication in the international journal Diabetes.

The study has also found that 49 among the 56 genes previously reported as associated with diabetes in other populations ' mainly white Caucasians are also observed in the Indian population.

But TMEM163, among all the candidate genes, appears to confer the highest risk of diabetes ' a person with a disease-associated variant of TMEM163 has 1.56 times higher risk of diabetes than a person without this variant.

A gene called TCF7L2 has until now shown the strongest association ' people with one variant of this gene have 1.51-fold higher risk of diabetes than people without that variant.

A senior endocrinologist who's a member of the consortium said that the new candidate gene and all the other known genes for diabetes explain only about eight per cent of the extra risk of diabetes among Indians.

"Diet and lifestyle appear to contribute far more to the risk of diabetes than genes ' so diet and exercise still remain a key to diabetes control," said Nikhil Tandon, professor of endocrinology at the All India Institute of Medical Sciences in New Delhi. "But the new gene is interesting because it opens a new avenue for research to understand underlying mechanisms of the disease."

"Decoding a new pathway for disease could eventually lead to new therapeutic strategies," said Samir Brahmachari, director general of the Council of Scientific and Industrial Research, IGIB's umbrella agency.

"This is significant for another big reason," Brahmachari said. "About 96 per cent of genome analysis studies looking for disease associations were based on white Caucasian populations. I've always said the Indian population would be an asset in genome analysis ' we now have solid evidence for this."

Doctors say the dramatic rise in the observed prevalence of diabetes in India over the past four decades reveals the dominance of diet and lifestyle factors over the genetic makeup. Surveillance studies suggest that diabetes prevalence has increased from less than 5 per cent in 1970s to about 18 per cent by 2010.

The Indian Diabetes Consortium is a joint research programme with scientists from more than a dozen institutions across the country, including the National Institute of Biomedical Genomics in Kalyani and the Indian Statistical Institute in Calcutta, and the Madras Diabetes Research Foundation in Chennai.