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
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
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.
Source: Wake Forest University Baptist Medical Center