Study On The Association Between 2 Type Diabetes Mellitus And Mutation In The Mitochondrial Gene

Object: Mitochondron is the special organ which stores and supplies energy for cells. Mitochondrial DNA is the only extra-chromosomal genome in human cells, which can replicate transcript and encode autonomously. The relationship between mitochondrial gene defect and the development of diabetes mellitus has been widely attended. In the study, 175 randomly selected, unrelated HuBei's patients with type 2 DM and 200 normal controls were included. 7 positions (np3243, 3251, 3264, 3290, 3316, 3394, 3593) in mtDNA tRN^Leu(UUR) gene and its adjacent region were screened, which were thought to be genetic hot spots for DM. The aim of this study is to investigate the prevalence of mtDNA gene mutations and find out the relation between mt DNA mutations and 2 type diabetes mellitus.Methods: One hundred and seventy-five patients with 2 diabetes mellitus without consanguinity and two hundreds controls with normal glucose tolerance and absence of DM family history. The mutation determined by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) and DNA sequencing. The function of the variants in tRNA^Leu(UUR) were predicted for minimal free energy secondary structures by RNA folding software mfold version 3.1. four nucleotide substitutions of mtDNA (np 3316, 3394, 3593, 3606) were Antherprot software screened.Results: In diabetic group , the point mutation of mitochondrial DNA 3394 T→C was found in 5 of 175 diabetes(2.9%), 6 (3.4%) of 3316 G→A mutation, 1 (0.6%) of 3290 T→C, 3593 T→C mutation respective. In controls, the point mutation 3316 G→A were found in 2 of 200 controls(l%); However, 3394 T→C mutation, 3290 T→C mutation and 3593 T → C mutation were not found. Not found 3243, 3264,3251 mutation in two groups. The 3606 A→G mutation neither appearing in MITOMAP database nor reported in literature before. No statistically significant associations were found in thefrequency of above mutation between two groups except 3394 T—*C mutation. The 3264 T—>C mutation caused a great alteration in the minimal free energy secondary structure mode. The 3394T—+C mutation results substitution at amino acid which influence interspace structure of ND1 gene.Conclusion: Mt DNA ND1 gene mutations at 3394 T—?C might contribute to the pathogenesis of DM with other genetic factors and environment factors in the HuBei's population.