Mitochondrial DNA variants linked to type 2 diabetes

Genetic variants in mitochondria, energy-producing structures harbouring DNA that are inherited only from the mother, are directly linked to metabolic markers for type 2 diabetes, according to a report published online recently in Genome Research.

According to the Centers for Disease Control, 7 % of the US 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, containing 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 strains could be attributed to variation in the mitochondria.

The researchers found that the two strains exhibited significant differences related to energy metabolism and storage. One rat strain showed impaired glucose tolerance, reduced muscle glycogen synthesis, decreased skeletal muscle ATP (energy) levels and decreased activity of the cytochrome c oxidase enzyme, 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. 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," said 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."

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).