title: Mitochondrial gene mutations in patients with insulin-dependent diabetes mellitus in Taiwan.
abstract: We studied the prevalence of mitochondrial gene mutations in subjects with insulin-dependent diabetes mellitus (IDDM) in a Chinese population living in Taiwan. Eighty-four subjects with insulin-dependent diabetes mellitus and 105 unrelated normal controls were recruited in the present study. Both an A-to-G mutation at position 3243 and a mutation at position 8,344 of the mitochondrial DNA were screened by polymerase chain reaction-restriction fragment length polymorphism methods and confirmed by direct DNA sequence analysis. The insulin secretory response was assessed by the C-peptide response to glucagon administration. Among 84 IDDM patients, two (2.4%) subjects were found to carry the 3,243 nucleotide pair (np) mutation. There was no np 8,344 mutation in this series. Of the two subjects carrying a mitochondrial gene mutation, case 1 manifested initially as gestational diabetes mellitus. Manifestation of case 2 was consistent with MELAS, a syndrome of mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes. The pancreatic beta cell reserve was reduced, as the glucagon-stimulated C-peptide response was very low in these two cases. HLA genotyping studies revealed that case 2 carried DRB1*0301-DQA1*0501-DQB*0201/ DRB1*0405-DQA1*0301-DQB1*0302, which was the most susceptible genotype to IDDM in our population. Anti-GAD65 antibody was also positive in this patient. In addition to the nuclear genes, a defective mitochondrial gene might contribute to some of the clinical cases with IDDM.
authors.affiliation: Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, R.O.C.
authors.forename: L M
authors.initials: LM
authors.lastname: Chuang
authors.forename: H P
authors.initials: HP
authors.lastname: Wu
authors.forename: W Y
authors.initials: WY
authors.lastname: Tsai
authors.forename: C S
authors.initials: CS
authors.lastname: Lai
authors.forename: T Y
authors.initials: TY
authors.lastname: Tai
authors.forename: B J
authors.initials: BJ
authors.lastname: Lin
mesh_terms: D000328:Adult; D004272:DNA, Mitochondrial / Q000235:genetics*; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D006680:HLA Antigens / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D015994:Incidence; D008297:Male; D009154:Mutation; D010375:Pedigree; D016133:Polymerase Chain Reaction; D015995:Prevalence; D013624:Taiwan / Q000453:epidemiology
chemical_list: D004272:DNA, Mitochondrial; D006680:HLA Antigens