IIT Madras team identifies gene that spurs Indian’s risk of diabetes, BP

An international team of researchers led by the Indian Institute of Technology (IIT) Madras has identified a gene/protein variation present among Indians and other South Asians that increased their risk of diabetes, heart attacks and hypertension.

The team found that the gene variation was present in approximately 15 per cent of Indian and other South Asian populations.

Further, people carrying this variant are 1.5 times more likely to have hypertension, type 2 diabetes, and coronary artery disease. This combination could account for the higher prevalence of metabolic diseases among Indians and other South Asians, according to the study published online in the peer-reviewed Diabetes journal.

Pancreastatin is a small part (peptide) of a protein called Chromogranin A (CHGA) found in mammals including humans. It exerts important physiological effects, mostly with respect to insulin release. It inhibits the release of insulin in the body in response to blood glucose/glucagon and drugs like sulphonylurea.

The IIT Madras team had earlier analysed the effect of this genetic variation on cardiovascular and metabolic disease states in a small Indian population (na%400). They found that variation was associated with higher plasma glucose levels.

In the latest study, the team extended the sample to a larger population (na%4300) and included people from South and North India.

They used a combination of experimental and computational modelling studies to “unravel the mechanistic basis for the higher activity of the variant peptide (PST-297S) in comparison to the wild-type peptide (PST-WT) and to account for the higher disease risk in the carriers of the 297Ser allele.”

The study showed that the variant peptide had a higher affinity to the insulin receptor in cells, which prevents insulin from binding to the receptor of the cells for glucose uptake. This results in a higher risk of insulin resistance and diabetes among people who carry the variant of this peptide.

“This study has implications in the area of diagnostics and personalised medicine. For example, our research findings may help in identifying individuals (at earlier stages of their lives — much before the onset of the disease- because the genetic make-up mostly remains unchanged throughout the life) who may be susceptible to Type 2 diabetes,” said Prof. Nitish Mahapatra from the Department of Biotechnology.

“This should be particularly useful for people with family history of cardiovascular and metabolic diseases for preventive healthcare and better management of disease,” he added.

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