A new mitochondrial DNA mutation associated with non-insulin-dependent diabetes mellitus.

Mitochondria play an important role in glucose-induced insulin secretion in pancreatic beta cells. We therefore examined whether patients with NIDDM exhibit genetic variability in mitochondrial DNA (mtDNA), a candidate gene for NIDDM. We sequenced mtDNA in the region encoding tRNALeu and the adjacent region in several diabetic patients with clinical features suggesting mitochondrial DNA mutations. We found a new point mutation at position 3316 that leads to an amino acid change in the ND-1 protein. The frequency of the mutation was screened with PCR-RFLP in 295 NIDDM patients and 406 controls. We found ten NIDDM patients (3.4%) harbored the mutation. Although 4 control subjects had the mutation, the frequency was significantly higher in the NIDDM patients than in the control subjects (p = 0.02). These results suggest that the 3316 mutation is associated with NIDDM.