Diabetes : Genes Predict Diabetes Risk

Seema Singh, Mint, New Delhi

In the largest study on Indian population, a team of researchers has shown eight most common genetic variants associated with type II diabetes, marking the first consolidated steps towards predictive diagnosis of a lifestyle disorder that affects at least 50 million people in the country.

Globally, some 22 genetic variants have now been associated with type II diabetes, but they have been studied mostly in the European population. In the present study, published in the journal Diabetes, a team led by Giriraj R. Chandak of the Centre for Cellular and Molecular Biology in Hyderabad, and D. Bharadwaj of the Institute of Genomics and Integrative Biology in New Delhi shows that while these eight variants are a subset of the 22, they show "larger effect" in the Indian population.

That is, these genes have a stronger association with diabetes when tested in Indian population. For instance, gene TCF7L2, known to predict 27% risk in many populations, has a much higher "odds ratio", and hence a larger effect, in the Indian population in comparison to Europeans, said Chandak.

The study involved 5,164 individuals, comprising 2,486 patients with type II diabetes of Indo-European ethnicity (north Indians) and 2,678 ethnically matched control subjects. All were recruited from Delhi and Pune.

Coincidentally, another study led by V. Mohan and Radha Venkatesan of the Madras Diabetes Research Foundation in a south Indian population sample has looked at the same set of genes. To be published in the journal Metabolism, this study finds similar association with type II diabetes. "We have also found that the TCF7L2 gene has the strongest association for type II diabetes," said Mohan, chairman and chief diabetologist, Dr Mohan's Diabetes Specialities Centre in Chennai.

Indians are diagnosed with diabetes a decade earlier and at a lower body mass index than Europeans. "There is a genetic signature in this but we don't know yet," said Bharadwaj. Through such studies, researchers are looking at markers that would eventually help in identification of high-risk groups even in childhood. "If we could tell people at a very early age that at 40 they are very likely to be diabetic and alter their lifestyle, we could push the onset of this disease by a few decades," he added.

Type II diabetes, characterized by high blood sugar, is the most common form of diabetes, and is increasingly believed to be a lifestyle disorder.

Next on the agenda of Indian researchers is a genome-wide association study, where they'd look for diabetes-associated genetic variations across the whole genome. Bharadwaj expects that the study, involving 10,000 people, will show newer genes in the Indian population when it gets completed by October.

These studies could predict the risk at a population level, but at an individual level the predictive value goes down. Researchers say they need more studies, of genes and their interplay with environment, and factors such as obesity in order to get good diagnostic markers.

Still, these findings come at a time when there are two schools of thought emerging in Indian diabetes research--one group suggests that Indians are "born to be diabetic"; others believe type II diabetes is essentially about "energy imbalance in the body".

In his research at King Edward Memorial Hospital and Research Centre in Pune, Chittaranjan S. Yajnik has shown that even at low birth weight Indians are fat. "Indians have more fat per kg of weight. This reflects in the chemistry of blood, which shows high levels of insulin and leptin, indicating higher risk factors for diabetes," said Yajnik. To test this in a nationwide population, he has formed a consortium of researchers. On the other hand, Bharadwaj's preliminary findings from an on-going study with schoolchildren point towards environmental factors. He thinks Indians are taking too many calories and expending too little.

As Mohan says, "Knowledge about the genetics of diabetes in Indians is just emerging."

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Copyright © 2010, Mint, New Delhi

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