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Gene for diabetes found


A gene involved in the action of insulin is associated with type 2 diabetes and the body’s response to insulin, report scientists at Wake Forest University Baptist Medical Center.

Donald W. Bowden, Ph.D., the principal investigator, and his colleagues described the gene in two articles in the November issue of Diabetes, a journal of the American Diabetes Association.

Bowden said the gene is called PTPN1 (Protein Tyrosine Phosphatase N1) and is found on the human chromosome 20, which has long been targeted by investigators as a likely site for diabetes genes. "The protein that this gene makes represses the insulin response, so if you are making a lot of this protein, your ability to respond to insulin would be blunted, which would lead to higher glucose (sugar) in your bloodstream. If it is too high, that’s diabetes," said Bowden, professor of biochemistry and internal medicine - endocrinology. The researchers found several variants of the PTPN1 gene, he said. "One common form is associated with diabetes, and there’s another common form that appears to be protective."

The risky variant of PTPN1 gene is found in about 35 percent of the Caucasian population and the protective form of PTPN1 is found in about 45 percent. The other variants are apparently neutral, neither enhancing nor reducing the risk of diabetes. "There are certainly other genes that contribute to diabetes," Bowden said. "This is good evidence for one." The researchers found a "remarkably similar pattern" in Hispanics. "In Hispanic families, people who had the risky form of the gene did not respond to insulin well and had higher levels of glucose in their blood – both risk factors for diabetes."

Bowden said the newly discovered gene could be a significant contributor to diabetes in Americans. With Josyf C. Mychaleckyj, "we’ve carried out calculations to try to assess how much of an impact the different forms of this gene have on diabetes in the population. The best guess right now is it contributes to about 20 percent of diabetes in Caucasian Americans."

But the picture becomes more complex in other racial groups. "The effect doesn’t seem to be there in African-Americans," Bowden said. Other genes may be responsible for diabetes in African-Americans, and the research team is pursuing those genes.

Bowden said the research was conducted in three population studies. The first group involved 300 Caucasian patients with type 2 diabetes and end-stage kidney disease, matched with 310 unrelated Caucasian subjects who do not have diabetes. The results were confirmed in a second completely independent group of 275 Caucasians with diabetes who are participating in the Diabetes Heart Study and a 200-person control group.

The third group was from the IRAS Family Study (Insulin Resistance Atherosclerosis Family Study), a national study in which Wake Forest investigators based in the Department of Public Health Sciences and the Center for Human Genomics are major contributors. The analysis focused on Hispanic IRAS participants and their families – brothers, sisters, fathers, mothers, and children. In 811 Hispanic participants in the study, the results "are completely consistent" with the results among Caucasians, Bowden said.

He said fifth-year graduate student Jennifer Bento used the latest genetic technologies to work through the entire region of chromosome 20, "genotyped hundreds of markers," and found the different forms of PTPN1.

Besides Bowden, Bento and Mychaleckyj, the team also included Nicholette D. Palmer, Leslie A. Lange, Carl D. Langefeld , Ph.D., and Stephen Rich. Ph.D. of Public Health Sciences and Barry I. Freedman, M.D., a nephrologist.

Karen Richardson | EurekAlert!
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