Molecular analysis of diabetes mellitus-associated A3243G mitochondrial DNA mutation in Taiwanese cases

Investigation of the clinical manifestations of MELAS-specific A3243G mitochondrial DNA (mtDNA) point mutation has suggested that the A3243G mutation of mtDNA can cause certain subtypes of diabetes mellitus (DM) and contributes about 0.15% of the overall incidence of diabetes. However, a relationship between the diabetic syndrome and the proportion of mutant mtDNA in affected tissues remains unclear. In this article, we report the results of our investigation of 14 diabetic and 23 non-diabetic patients who had the A3243G mutant mtDNA. The proportions of mutant mtDNA in different tissues were noted to change variably and neither heteroplasmy of mutant mtDNA in various tissues nor the proportion of mutated mtDNA in a specific tissue showed a correlation with the clinical phenotype of DM. Generation of a diabetic syndrome was not predictable from either the content of mutant mtDNA in leukocytes, hair follicles, or in muscle tissues. Further study showed that muscle tissue has the highest proportion of mutant mtDNA followed by hair follicles and by blood cells. Moreover, we observed that as the patient's age increased, all tissue showed a declining proportion of mutant mtDNA. These findings suggest that age may play a role in the manifestation of diabetes in patients with A3243G mutation of mtDNA.