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Scientists show that mitochondrial DNA variants are linked to risk factors for type 2 diabetes

14.08.2007
Today, researchers report for the first time that genetic variants in mitochondria—energy-producing structures harboring DNA that are inherited only from the mother—are directly linked to metabolic markers for type 2 diabetes.

The study, which highlights the role of mitochondrial genome variation in the pathogenesis of common diseases, is published online in Genome Research (www.genome.org).

According to the Centers for Disease Control, 7% of the U.S. population has diabetes, and 90-95% of those cases are classified as type 2 diabetes. Type 2 diabetes is caused by external factors such as diet and exercise, and is influenced by several genes. While most of the genes known to be involved in diabetes susceptibility are located in the nuclear genome, a recent study estimated that more than 20% of type 2 diabetes cases may involve mutations in the mitochondrial genome.

In the study published today, the scientists compared two different rat strains; the strains possessed virtually identical nuclear genomes but different mitochondrial genomes. This eliminated any complicating effects due to environmental factors or variation in the nuclear genome. Any differences observed between the two rat strains could be attributed to variation in the mitochondria.

When comparing the two rat strains, the researchers found that the two strains exhibited significant differences related to energy metabolism and storage. One rat strain exhibited impaired glucose tolerance, reduced muscle glycogen synthesis, decreased skeletal muscle ATP (energy) levels, and decreased activity of an energy-producing enzyme called cytochrome c oxidase, when compared to the second rat strain. These metabolic characteristics are typical of diabetic individuals.

The researchers then obtained DNA sequences from mitochondria of both rat strains, and found DNA variants in genes that encode for proteins involved in energy production. Thus, for the first time, they were able to directly link inherited variation in the mitochondrial genome to metabolic markers for type 2 diabetes.

“Our study highlights the role of mitochondrial DNA variation in common genetic diseases,” says Dr. Theodore Kurtz, the lead investigator on the project. “In addition, the animal models developed in this study will open the door for future studies in which the effects of mitochondrial genome variation can be investigated on fixed nuclear genetic backgrounds.”

Maria Smit | EurekAlert!
Further information:
http://www.cshl.edu
http://www.genome.org
http://www.cshlpress.com

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