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OU Genetic Discovery Points to Diabetes Susceptibility Gene

Tuesday, February 05, 2013 - Campus News - Contact Theresa Green, (405) 833-9824

A University of Oklahoma researcher is among a team of scholars that has identified a gene that may predispose people to Type 2 Diabetes.

"Diabetes is not a simple disease," said Dr. Dharambir K. Sanghera, a genetics researcher with the OU College of Medicine's Department of Pediatrics. "It was considered that it was only a lifestyle disease; that it was caused by the way we eat," she said.

High fat diets were implicated, but doctors then noticed that diabetes was common among people who ate low-fat diets too. In fact, it was more common in some of these groups.

While diabetes is prevalent among six percent of white populations, the incidence is significantly higher among Latino (17 percent) and South Asian (20 percent) populations.

For a decade, Sanghera, director of the Molecular Genetic Epidemiology Laboratory at the OU Health Sciences Center, has joined other researchers in the search for a gene that causes Type 2 Diabetes. Now, they may have found it.  It's a discovery that marks quite a change from the commonly held beliefs about diabetes 30 years ago. Then, Sanghera said few thought diabetes was genetic in origin.  "We now know that diabetes is not only a lifestyle disease," Sanghera said. "It is also genetic, and there is a strong interaction between genes and lifestyle." However, finding the gene or genes that trigger diabetes is a complex task. Most studies have focused upon diabetes among Europeans. However, in a new paper, Sanghera and fellow researchers present the results of their genome-wide association study (GWAS) on a group of Punjabi Sikhs from northern India.

Unlike certain other groups, the Sikhs are largely free from traditional risk factors such as smoking, obesity and a diet heavy in meats. For religious and cultural reasons, Sikhs do not smoke or chew tobacco, and about half of them are lifelong vegetarians. Nevertheless, the prevalence of Type 2 Diabetes among the Sikhs is greater than 20 percent.
The GWAS found what Sanghera calls a "locus" among the 7329 Sikhs studied. That is they found a particular gene, called SGCG, which was strongly associated with a susceptibility to Type 2 Diabetes.

"We are thinking this is the gene that might be causing diabetes," she said. However, she noted the study can only claim to have found a high correlation--not a causal relationship--between the gene and diabetes.

"It means that more studies are needed to further dissect this gene," Sanghera explained.

While her study is the first to report on the SGCG gene and its association with diabetes, Sanghera said that other scientific studies have identified some 60 different genes that could also cause Type 2 Diabetes.

"The problem at this time is that there are a lot of genes and they are in interaction with each other as well as with life-style factors," she said, adding that the focus on the role of genetics in diabetes does not mean that life-style factors are irrelevant.

"If 50 percent of the contribution is genes, then 50 percent of the contribution is lifestyle and environment." Sanghera said.
Dr. Timothy Lyons, director of research and scientific programs at the Harold Hamm Diabetes Center, said that while  it has been known that Type 2 diabetes runs strongly in families, finding the genes responsible has proven challenging, in part because not just one or two, but many genes are involved. And while this research identified a gene that confers risk specifically in the Sikh community in India, the implications may be of importance to everyone else as well.

"An understanding of this newly identified gene may shed light on the mechanisms underlying Type 2 diabetes. Understanding these mechanisms is an essential step in the quest for a cure for diabetes," he said.

Lyons stressed the discovery does not undermine current thought on preventing Type 2 diabetes through lifestyle changes and treatments tailored specifically to each patient.

"Lifestyle modification is the most effective way to prevent Type 2 diabetes. However, this study demonstrates that the fight against diabetes in specific ethnic groups may have to go beyond our current focus on prevention," said Dr. Sanjay Bidichandani, CMRI Claire Gordon Duncan Chair in Genetics, OU College of Medicine. 

As studies continue, Sanghera believes that population-specific gene discoveries like theirs offer a glimpse of personalized medicine in the future.

"The importance of these findings is that the discovery of new gene-based targets will simplify the use of patients' genetic variations and allow for the selection of drug therapies tailored to their own genetic profile," she said.

The research appears in the journal Diabetes. The study was sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases of National Institutes of Health. 

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