Gene variants may increase susceptibility to type ...( For years scientists have known t...)

For years, scientists have known that single-gene mutations, most affecting beta cell function, contribute to rare forms of diabetes, including the six types of Maturity Onset Diabetes of the Young or MODY. Such mutations account for about 2 to 3 percent of all diabetes cases. A mutation in the coding region of HNF4A causes MODY type 1, a rare form of diabetes that begins before age 25 in people of normal weight.

Unlike MODY, however, type 2 diabetes usually begins after age 40 in overweight, inactive people and is more common in those with a family history of diabetes. In the United States, type 2 diabetes disproportionately affects African Americans, Hispanic/Latino Americans, and American Indians. Affecting about 17 million people nationwide, this form of diabetes accounts for 90 to 95 percent of all diabetes cases in the U.S. Its prevalence has been steadily rising in the past 30 years, and it is increasingly being seen in younger people, even in children. Hallmarks of the disease are insulin resistance--the inability of target tissues to respond to insulin--and a gradual failure of beta cells to produce enough insulin.

Scientists have come a long way in understanding the basis for diseases arising from single-gene mutations. Understanding the genetic basis of the more common, polygenic diseases such as diabetes has been much more difficult.

"We could have scoured the coding region of every gene on chromosome 20 by sequencing it in many patients and not come up with anything," Dr. Permutt noted. "That's because the problem isn't in the gene itself but in a regulatory region far from the gene. This study suggests that perhaps the level of expression of candidate genes will expand our understanding of genetic risk factors. It also shows us that if we scrutinize the gene itself from beginning to end, we haven't done a complete job. We need to look at polymorphic markers surrounding the gene for differences in those m
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Contact: Geoff Spencer
spencerg@mail.nih.gov
301-402-0911
NIH/National Human Genome Research Institute
11-Mar-2004