IIT Madras identifies gene/protein variation in Indians & other South Asians that increases risk of metabolic diseases

The team of researchers found that this variation was present in approximately 15 per cent of Indian and other South Asian populations

An Indian Institute of Technology Madras-led International Research Team has identified a gene/protein variation present among Indians and other South Asians that increased their risk of diabetes, heart attacks and hypertension.

This team of researchers found that this variation was present in approximately 15 per cent of Indian and other South Asian populations. The researchers also found that 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.

The Research was led by Prof. Nitish R. Mahapatra, Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, IIT Madras. The Research Paper was co-authored by researchers from International Research Institutions including Lerner Research Institute, Cleveland Clinic, U.S.; Joslin Diabetes Center, Harvard Medical School, U.S.; University of Maryland Baltimore School of Medicine, U.S; and Indian Institutions including CSIR-Central Drug Research Institute, Lucknow;  Dr. ALM PG Institute of Basic Medical Sciences, University of Madras, Chennai; Postgraduate Institute of Medical Education and Research, Chandigarh; Madras Medical College and Government General Hospital; Madras Medical Mission; Madras Diabetes Research Foundation, and National Brain Research Centre, Haryana.

Explaining the key findings of this research, Prof. Mahapatra said, “South Asians are at greater risk of cardiovascular and metabolic diseases. Besides environmental factors our genetic architecture is believed to be responsible for this observation. However, the key genetic variants that enhance our disease risk remain poorly understood. Our study identified one key genetic risk factor for cardio-metabolic diseases. We also discovered the molecular basis for the enhanced disease risk in people who carry this mutation in their genomes.”

Elaborating on the practical applications of this research, Prof. Mahapatra said, “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. This should be particularly useful for people with family history of cardiovascular and metabolic diseases for preventive healthcare and better management of disease.”

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

Prof. Nitish Mahapatra added, “We extended our sample to a larger population (n≈4300) and included people from South and North India. Our research team 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.”