Gene variations can influence risk of obesity

Even small genetic variations can increase the risk

May 19, 2018 09:27 pm | Updated 11:13 pm IST

A team of researchers from New Delhi have found an explanation for why one sibling may develop obesity faster than the other though brought up under similar home environment with almost similar diet and habits.

The team analysed the genetic variations in genes of over 3,500 urban school going children (11-17 years) and found certain alterations in two genes — ARID1A and KAT2B — that can delay or hasten the process of obesity development with respect to the daily habits.

“We analysed the variations in 35 chromatin modifier genes. This is one of the groups of genes that signals the healthy and unhealthy habits to the body. In response to your habits (overeating, sedentary lifestyle, exercise) these genes modify the architecture of DNA and its associated protein-complex called chromatin leading to change in expression of several biomolecules responsible for obesity development,” explains Anil K Giri, first author of a paper published in Scientific Reports, from Institute of Genomics and Integrative Biology. These two genes need to be further analysed to fully understand the mechanism of obesity development in adolescents.

The study was carried out in two stages. In the first stage, 1,283 adolescent boys and girls divided into two groups based on their BMI — normal weight and obese/overweight were studied.

Blood sample was collected and DNA was isolated. Using bioinformatics tools, the team studied the genes and looked for any variations. A total of 179 variations in the 35 chromatin modifier genes were tested for their role in obesity. Twenty-eight variations in 13 genes were found to confer risk with overweight. To further validate the findings additional 2,247 adolescents were studied in the second phase.

Finally, a comparative analysis showed significant associations of two variants in the ARID1A gene and one variation in the KAT2B gene. The ARID1A gene regulates transcription of many genes that influence metabolism while the latter has been reported to code for a protein that controls bodyweight & hyperglycemia in mice.

“The variation in the gene increases the obesity risk by enhancing the effect of environmental factors. Several environmental factors like sedentary lifestyle, junk food can further increase the risk independently. We have found just few gene variations. Many more to be explored,” says Anil

“The study was primarily carried out on Indian adolescents of Indo-European origin. Diet of the western population is different from ours and we are predominantly starch eating people. Diet has been known to play a direct role in influencing genes related to obesity” explains Prof. Dwaipayan Bharadwaj from CSIR-IGIB and corresponding author of the paper who is currently working at JNU. “Most of the obesity measures in our study were significantly associated with these three variants. Every human behaviour is dependent on the gene-environment interaction in some form or other. We are now working on understanding the various facets of the environment.”

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