Gene Mutation Affects 10% of People with Type 2 Diabetes


Mutation of a gene called HMGA1, which is associated with type 2 diabetes, is found in nearly 10 percent of people of white, European descent, according to a new study appearing in the March 2 issue of the Journal of the American Medical Association. This discovery may assist researchers in developing new treatments or act as an early indicator of insulin resistance and type 2 diabetes, among other advantages.

Mutation discovery may benefit type 2 diabetics

Type 2 diabetes mellitus, which represents up to 95 percent of all cases of diabetes, affects about 250 million people around the globe. In the United States, it is estimated that 25.8 million children and adults have diabetes, or 8.3 percent of the population.

The World Health Organization notes that nearly 3 million deaths each year are associated with diabetes, and millions more people experience life-altering complications from the disease, including kidney disease, cardiovascular disease, diabetic retinopathy, neuropathy, and amputation.

Insulin resistance is both a significant predictor and feature of type 2 diabetes, and heredity appears to be a major player in insulin resistance. However, scientists have been unable to identify the common genetic causes of insulin resistance. The protein HMGA1 is known to have a part in insulin receptor gene expression.


Therefore, a team of researchers from the University of Catanzaro in Italy examined the relationship between HMGA1 gene mutations and type 2 diabetes. The study participants included individuals with type 2 diabetes from Italy (3,278 patients), the United States (970), and France (354). Four control groups (two for the Italian study totaling 3,328; 958 in the US, and 50 in France) were also part of the study. For all the participants, genomic DNA was directly sequenced or analyzed for specific HMGA1 mutations.

The most common functional HMGA1 mutation was IVS5-13insC, which was identified in 7 to 8 percent of all participants who had type 2 diabetes. However, presence of the gene mutation varied among the groups. For example, the mutation was seen in 7.23 percent of type 2 diabetics in the Italian group versus 0.43 percent in one control group and 3.32 percent in the other control group. Among the diabetics from the United States, the mutation occurred in 7.7 percent versus 4.7 percent of controls. In the French population, the mutation appeared in 7.6 percent of patients and 0 percent of controls.

In addition to the IVS5-insC variant, the investigators also found three other functional mutations in the Italian population. When they considered all four variants, HMGA1 mutations accounted for 9.8 percent of the Italians who had type 2 diabetes and 0.6 percent of controls.

The authors of the study concluded that “variants in the HMGA1 gene are associated with type 2 DM [diabetes mellitus] in individuals of white, European descent.” They noted that, with additional research into variants of the HMGA1 gene, researchers may uncover significant clinical implications associated with the gene mutations, including new therapies, ways to predict therapeutic response, and their use as early predictors of insulin resistance and type 2 diabetes.

American Diabetes Association
Chiefari E et al. JAMA 2011; 305(9): 903-12
World Health Organization