Mitochondrial gene variation in type 2 diabetes mellitus: detection of a novel mutation associated with maternally inherited diabetes in a Chinese family

Objective To explore the relationship between type 2 diabetes mellitus and the mutation(s) in mitochondrial DNA. Methods According to the previous literature, the fragment of mitochondrial DNA from nucleotide 3153 to 3551, which had shown high frequency of point mutation, was scanned with the technique of polymerase chain reaction - sin gle strand conformation polymorphism (PCR-SSCP) in Chinese normal control, type 2 diabetic population, and 12 families suffered from maternally inheri ted type 2 diabetes mellitus. Direct sequencing was applied to detect the f ragments with abnormal conformation. Results No special band was found in SSCP electrophoreses in Chinese normal control, and only one subject (No, 81) of diabetic population indicated th e abnormality in SSCP study, which was affirmed to be a silent point mutati on of T to C at nucleotide 3336 inducing no change in amino acid (ATT-->ATC , lie). Pedigree 25 001 was the only family that exhibited strongly differe nt SSCP characteristic from the other 11 ones, which was confirmed to be ca used by a single point mutation mt3285T-->C/T in the coding region of tRNA( Leu)((UUR)) gene by the technique of direct sequencing. of direct Conclusions The variation within mt DNA 3153 3551 is not the major cause of type 2 diabetes in Chinese population suffered from this disease in this s tudy. The point mutation T-->C/T at the mitochondrial nucleotide 3285, whic h was found in pedigree 25 001, is located in the highly conservative regio n of tRNA(Leu(UUR)) gene. It is strongly suggested that this mutation cause the conversion in the 3-dimentional structure of tRNA(Leu(UUR)), which mig ht disturb the normal translation and lead to the impairment in mitochondri al oxidative phosphorylation characterized by the defects of the polypeptid es involved in the respiratory chain. Thus, insulin secretion deficiency an d insulin resistance might occur.