A NEW MITOCHONDRIAL-DNA MUTATION ASSOCIATED WITH NON-INSULIN-DEPENDENT DIABETES-MELLITUS

Mitochondria play an important role in glucose-induced insulin secreti on in pancreatic beta cells. We therefore examined whether patients wi th NIDDM exhibit genetic variability in mitochondrial DNA (mtDNA), a c andidate gene for NIDDM. We sequenced mtDNA in the region encoding tRN A(Leu) and the adjacent region in several diabetic patients with clini cal features suggesting mitochondrial DNA mutations. We found a new po int mutation at position 3316 that leads to an amino acid change in th e ND-1 protein. The frequency of the mutation was screened with PCR-RF LP in 295 NIDDM patients and 406 controls. We found ten NIDDM patients (3.4%) harbored the mutation. Although 4 control subjects had the mut ation, the frequency was significantly higher in the NIDDM patients th an in the control subjects (p=0.02). These results suggest that the 33 16 mutation is associated with NIDDM. (C) 1995 Academic Press, Inc.