HLA-DQ polymorphism and degree of heteroplasmy of the A3243G mitochondrialDNA mutation in maternally inherited diabetes and deafness

Aim Maternally inherited diabetes and deafness (MIDD) associates with a mut ation at position 3243 in mitochondrial DNA. Phenotypic expression of MIDD includes Type 1-like and Type a-like diabetes. This study examined whether HLA-DQ phenotype and the degree of heteroplasmy in leucocyte and oral mucos a DNA influence clinical expression of the 3242 mutation. Methods In a group of 20 unrelated probands with MIDD, eight with Type 1-li ke diabetes, 12 with Type 2-like diabetes, HLA-DQ type and degree of hetero plasmy for the 3243 mutation were determined. HLA-DQA1/DQB1 phenotypes were categorized as predisposing, neutral or protective for autoimmune-mediated Type 1 diabetes. Results No differences were observed between Type 1 and Type 2-like MIDD gr oups with respect to the cumulative frequency of protective and predisposin g HLA-DQ types. Predisposing HLA-DQ types are more prevalent in MIDD patien ts than in the control population (P < 0.05). Degrees of heteroplasmy for t he 3243 mutation showed large variations in patients, ranging from 1 to 52% in leucocyte DNA. A strong correlation was seen between heteroplasmy in le ucocyte DNA and DNA from oral mucosa cells (r = 0.89, P < 0.001). No correl ation was observed between the degree of heteroplasmy and diabetic phenotyp e, even when group size was extended with diabetic relatives of patients wi th MIDD. The age of diagnosis of diabetes was not correlated with heteropla smy, but the degree of heteroplasmy tended to decrease with age. Conclusions The phenotype of diabetes in MIDD appears to be independent of HLA-DQ phenotype and degree of heteroplasmy in leucocyte and oral mucosa DN A indicating that other, as yet unknown, factors modulate clinical expressi on of the 3243 mutation.