IIT-M research teams discover protein that increases diabetes risk in Indians

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An international research team led by the Indian Institute of Technology, Madras (IIT-M) has identified a gene/protein variant present in Indians and other South Asians that increases their risk of diabetes, heart attack and of hypertension.

The study found that 15% of Indian populations and other South Asian populations have this variation, people with this variant are 1.5 times more likely to suffer from hypertension, type 2 diabetes and disease coronary.

“This combination could explain the higher prevalence of metabolic diseases among Indians and other South Asians,” said the study, the results of which were published online in “Diabetes,” the American Diabetes Association’s flagship journal. .

The research was led by Professor Nitish R Mahapatra, Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, IIT-M, while the research was co-authored by several others.

“South Asians are at greater risk for cardiovascular and metabolic disease. Besides environmental factors, our genetic architecture would be responsible for this observation. However, the main genetic variants that increase our risk of disease remain poorly understood. Our study has identified a key genetic risk factor for cardio-metabolic diseases,” Prof Mahapatra said.

He said the study had implications for the field of diagnostics and personalized medicine and that the research results could help identify individuals (at earlier stages in their lives – long before the onset of the disease – because the genetic makeup remains virtually unchanged throughout life) which may be susceptible to type 2 diabetes.

“This should be especially helpful for people with a family history of cardiovascular and metabolic disease for preventative health care and better disease management,” he added.

Pancreatin is a small part (peptide) of a protein called chromogranin A (CHGA) found in mammals, including humans. It exerts important physiological effects, mainly with regard to the release of insulin. It inhibits the release of insulin in the body in response to blood glucose/glucagon and drugs like sulfonylurea, IIT-M said.

The team had previously analyzed the effect of this genetic variation on cardiovascular and metabolic disease states in a small Indian population (n≈400). They found that the variation was associated with higher plasma glucose levels.

“We extended our sample to a larger population (n≈4300) and included people from southern and northern India. Our research team used a combination of experimental and computational modeling studies to unravel the mechanistic basis for the higher activity of the variant peptide (PST-297S) compared to the wild-type peptide (PST-WT) and to hold account for higher disease risk in carriers of the 297Ser allele,” he said.

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