NZ scientists untangling obesity and diabetes’ ‘missing link’

Genetic changes hidden among our so-called junk DNA have helped New Zealand scientists uncover a suspected missing link between type 2 diabetes and obesity.

Nearly a third of Kiwis live with obesity, which is considered a major risk factor for type 2 diabetes and other disorders.

The fact obesity and diabetes so often affect the same people has led scientists to suspect that similar genes are contributing to the development of the disorders, which are both on the rise around the world.

A just-published study by Kiwi researchers has revealed how certain genetic changes found in regions of DNA that are non-coding and associated with the disorders can act together to alter how genes behave.

Techniques developed in the new study could provide medical researchers with new information and a fresh way to attack the puzzle, which may lead to better treatment, or even prevention, of the disorders.

The study, led by Dr Justin O’Sullivan, a molecular biologist at the University of Auckland’s Liggins Institute, focused on regions of DNA that commonly vary between individuals and that have been linked to a disease.

Called single nucleotide polymorphisms, or SNPs, some of these fall inside genes, but most fall outside them, in segments once believed to be little more than inactive spacers between genes.

It was believed SNPs outside genes were brought into contact with, and influenced the working of, far-off genes through the way DNA was tightly coiled inside the cell nucleus.

“SNPs offer a key to unlock the riddles of many diseases and disorders that can be passed from parent to child, but do not seem to pass directly through O’Sullivan said.

SNPs that predisposed people to obesity were different from the ones linked to diabetes. But the Auckland team revealed there were many instances where an SNP for obesity and an SNP for diabetes were both in contact with, and changed the functioning of, the same gene.

“We can’t tell from this study if the SNPs themselves are causing the disorders through changing the way the genes work, or if it is something nearby on that same DNA segment,” said study co-author and Liggins PhD student Tayaza Fadason.

“But it is clear that these SNPs we have identified are markers of DNA segments that are somehow altering

SNPs offer a key to unlock the riddles of many diseases and disorders . . .

the genes,” the functioning of the genes they come into contact with.”

O’Sullivan pointed out another remarkable finding of the study, just published in the international journal Frontiers in Genetics.

“Many of the regulatory SNP-gene connections we pinpointed affect body tissues not usually thought of as driving obesity or type-2 diabetes — breast tissue, brain tissue from the cerebellum, skin and blood, the fat that sits just beneath the skin.”

This suggested researchers may need to broaden their hunt for genetic drivers of obesity and diabetes beyond “the usual suspects”, he said.

The study comes as Diabetes NZ this week launches its Diabetes Action Month.

Dr Justin O’Sullivan