Abstract

BACKGROUND
There are a few genes with proven potential for causing some form of NIDDM, These include the insulin gene, the insulin receptor gene, a gene linked to the adenosine deaminase gene on chrornosome 20, and the glucokinase gene. Recently, an A to G transition at position 3243 in transfer ribonucleic acid ""' ' was reported in maternally inherited NIDDM patients in Japan, it was reported that approximately 1% of diabetes patients have the 3243 bp point mutation. In this study we examined the positive rate and clinical characteristics of Korean NIDDM patients with mitochondrial DNA point mutation. METHODS: We screened randomly selected 433 NIDDM patients (rnale 221, female 212) from the diabetes clinic of Seoul National University Hospital regardless of age of onset, family history of diabetes, mode of' therapy, or any other clinical characteristics. Genomic DNA was extracted from pheripheral lymphocytes. To detect the 3243 bp mutation, PCR was carried out using mtDNA primers(2928-2947, 3558-3539) and then, PCR products were electro-phoresed on a 2%: agarose gel after digestion with the restriction endonuclease Apa-I. When electrophoretic results showed two or three bands, we confirmed mtl)NA 3243 bp point rnutation by DNA sequencing. RESULTS: Of the 433 Korean NIDDM patients, 5 patiients had mtDNA point mutation digested by restriction endonuclease Apa I. Only two patients (OA6%) had heteroplasmic point mutation at nucleo-tide 3243. The remaining three patients(0.69%) with homoplasmic point mutation at nt 3426 were inciden-tally discovered during procedure in detecting 3243 bp point mutation. This 3426 point rnutation had the same adenine to guanine point mutation as 3243 point mutation digested by Apa I and therefore was confused with 3243 point mutation by RFLP method. Two patients with 3243 points mutation, aged 39 and 32 years, BMI 17.0 and 14.4(kg/m), had neither hearing impairrnent nor family history of diabetes. They required insulin for the control of their hyperglycemia and their C-peptide levels less than 1.Ong/mL showed insulin dependent tendency. On the contrary, three patients with 3426 bp point mutation, aged 71, 70, and 62 years, BMI 28.0, 23.0, and 22.6 (kg/m2 ), showed their C-peptide levels 5.4ng/mL and 3.%g/mL and insulin resistant diabetes mellitus. CONCLUSION: Two kinds of point mutation were found in the mtDNA at position nt 3243 and nt 3426, and their incidence were 0.46%(2/433) and 0.69% (3/433) respectively. 3243 point mutation was associated with insulin deficient diabetes mellitus whereas 3426 point mutation insulin resistant diabetes mellitus. 3426 point mutation has the same adenine to guanine transition as 3243 point mutation restricted by Apa I and so, DNA sequencing is warranted to differentiate with 3426 from 3243 point mutation.

• Keywords: MtDNA 3243bp point mutation;MtDNA 3426bp point mutation;Diabetes Mellitus;