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Researchers at the University of Maryland School of Medicine Identify Genes That May Increase Risk of Type 2 Diabetes

Tuesday, December 11, 2007

 Dr. Alan Shuldiner's work with the Old Order Amish is yielding great discoveries.

Scientists use new approach to analyze DNA of Old Order Amish in Lancaster County, Pa.

Researchers at the University of Maryland School of Medicine have identified a number of genes in the Old Order Amish in Lancaster County, Pa., that may play a role in increasing the risk of Type 2 diabetes. They are publishing the results of their study in the December issue of the journal Diabetes and are making their entire set of data available online to other scientists to facilitate the search for common diabetes genes. The findings are important because they may hold clues to identifying individuals who are most at risk of developing Type 2 diabetes – a key factor in preventing and treating the disease.

University of Maryland scientists used a new approach called a genome-wide association study, or GWAS, to rapidly scan nearly 100,000 markers in the DNA of more than 500 members of the Amish community to find genetic variations associated with Type 2 diabetes. While this technique has been used recently to track down genes associated with many diseases, including Parkinson’s disease, cardiovascular disease and rheumatoid arthritis, this study was one of the first to employ the approach for Type 2 diabetes.

"This new approach enables us to uncover genes that have previously eluded us," says Alan R. Shuldiner, M.D., professor of medicine and head of the Division of Endocrinology, Diabetes and Nutrition at the University of Maryland School of Medicine who is the senior author of the study funded by the National Institutes of Health. "Within the last six months, the field of complex disease genetics has undergone a revolution in terms of discovering new genes and understanding the genetic basis of common adult-onset diseases."

In Type 2 diabetes, the body either makes too little insulin or doesn’t use it properly to convert blood glucose into energy. More than 100 million people are affected worldwide. The exact cause is unknown, but genetics and environmental risk factors, such as diet and physical inactivity, play a critical role.

Dr. Shuldiner, who directs the Program in Genetics and Genomic Medicine at the University of Maryland School of Medicine, says his group identified 94 regions on various chromosomes that appear to be associated with Type 2 diabetes in the Amish and at least one other population. They compared their findings with data from other recent genome-wide studies of the Pima Indians, Mexican-Americans in Texas and Caucasians in the Framingham (Mass.) Heart Study and a separate study in Finland.

A gene on chromosome 7 called GRB10 (growth factor receptor-bound protein 10), which inhibits how insulin controls blood glucose levels, showed a strong association with Type 2 diabetes in the Amish. "We’re particularly excited about GRB10. This is the first genome-wide association study that has identified GRB10 as a potentially important diabetes gene," says Coleen M. Damcott, Ph.D., an assistant professor of medicine at the University of Maryland School of Medicine and a co-author of the study. She adds that earlier studies by researchers at the University of Maryland and in Italy had found evidence of a possible link between this gene and a person’s risk of developing Type 2 diabetes.

Dr. Shuldiner has studied the Old Order Amish in Lancaster County, Pa., since 1993, searching for genes that cause not only diabetes but also other health problems, such as cardiovascular disease, osteoporosis, obesity and high blood pressure. More than 4,000 members of the Amish community have taken part in University of Maryland genetic studies, and the research is ongoing.

The Amish are ideal for such research because they are a genetically homogenous people who trace their ancestry back 14 generations to a few individuals who came to the United States from Europe in the mid-1700s. They also have large families, keep detailed genealogical records and have similar rural lifestyles.

In this latest study, researchers studied the DNA of 551 members of the Old Order Amish community, scanning across the entire genome for changes known as single nucleotide polymorphisms, or SNPs. They analyzed 82,484 of these genetic variations and came up with a number of genes they believe may be associated with Type 2 diabetes. Ninety-four SNPs were also associated with Type 2 diabetes in at least one of the four other study groups used for comparison.

More investigation is needed to confirm these findings, says the study’s lead author, Evadnie Rampersaud, M.S.P.H., Ph.D., a former postdoctoral fellow at the University of Maryland School of Medicine who is now at the University of Miami. To promote collaboration, University of Maryland researchers are making their data available to other scientists online at
"We’re now in an age where there needs to be collaboration among scientists to get answers. This data will be most useful if it is shared because other researchers are grappling with the same issues," Dr. Shuldiner says.

For more information about Dr. Shuldiner’s research with the Old Order Amish, go to www.medschool.umaryland.edu/amishstudies/index.asp.

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