UF Scientists Confirm Three Genes Linked To Diabetes

August 21, 1996

GAINESVILLE—University of Florida researchers are making steady progress in solving one of nature’s most challenging genetic puzzles: finding the intricate bits of DNA that make some people susceptible to developing insulin-dependent diabetes.

The task is particularly complicated because 10 genes or more may play a role. So far, only a few of the culprit genes have been mapped.

A team of scientists led by UF geneticist Jin-Xiong She has narrowed the search for several of those elusive genes by confirming the location of three genes linked to diabetes. Two of the genes were suggested by other researchers and a third was suspected by She and his colleagues. The genes are known, respectively, as IDDM4, IDDM5 and IDDM8.

Research results were published this summer in the journal, Human Molecular Genetics.

Locating the genes is more than an academic exercise. The knowledge will aid researchers in understanding how and why diabetes develops.

“The earlier research was not backed by enough data to conclude that the genes were associated with diabetes,” said She, who is an assistant professor of pathology, immunology and laboratory medicine and is affiliated with the UF College of Medicine’s Center for Mammalian Genetics.

She studied DNA samples from hundreds of families worldwide who have two siblings with insulin-dependent diabetes. Armed with maps depicting the location of known genes and other markers on DNA strands, he was able to identify patterns of inheritance and mathematically determine the chromosome regions where the genes associated with diabetes are located. Additional work is needed to pinpoint their precise position.

Numerous headlines touting discoveries have appeared since the federally funded Human Genome Project was launched nearly a decade ago to inspire researchers to determine the location and role of the total complement of more than 50,000 human genes. But they have been slow in coming for complex diseases associated with more than one gene, such as diabetes.

People with diabetes may have any one or more of what are known as “susceptibility genes”–genes that do not directly cause a disorder. Instead, these genes appear to render a person vulnerable to environmental forces, such as a virus, that trigger a debilitating strike on insulin-producing cells, leaving them unable to process the vital form of sugar known as glucose. Though it is possible to have many of the genes and never develop the disorder, the greater the number, the higher the likelihood of getting it.

Further complicating the matter, She said, other genes appear to protect people from diabetes–even if they have inherited the susceptibility genes.

“Once we know the genes that are involved, we hope to come up with new treatments and continue efforts to prevent diabetes,” She said. Eventually, genetic screening is expected to help target prevention efforts to individuals most at risk.

UF researchers are investigating strategies to delay or prevent insulin-dependent diabetes. They include giving insulin injections or oral insulin capsules to selected patients thought to be at risk for the disease.

More than 750,000 Americans have the insulin-dependent form of the disorder, which can be accompanied by lifelong medical complications such as heart disease, blindness, kidney failure and poor circulation in the lower limbs.