title: [Association of mitochondrial DNA variation with type 2 diabetes mellitus].
abstract: OBJECTIVE
  To explore the prevalence of mitochondrial DNA (mtDNA) mutations in patients with type 2 diabetes mellitus in Hubei.
  
  
  METHODS
  A total of 184 cases of type 2 diabetes mellitus and 210 matched healthy controls with normal glucose tolerance were recruited for the study. The variants of mtDNA, including MIND13316 (G-->A), MIND13394 (T-->C), MTTE14693 (A-->G), MTTL1 3243 (A-->G), MTRNA1310 (C-->T) and 16189 (T-->C), were screened using PCR-restriction fragment length polymorphism (PCR-RFLP) analysis and DNA sequencing. The mutations were analyzed by mfold or tRNAscan-SE softwares.
  
  
  RESULTS
  The mutation rates of 3316 (G-->A), 3394 (T-->C), 14693 (A-->G) were 3.26%, 2.72% and 2.17% respectively in type 2 diabetes group, whereas in the control group, the point mutations of 3394 (T-->C) and 14693 (A-->G) were not detected, but two subjects with 3316 (G-->A) were found (0.99%). There were significant differences in mutation rates of 3394 (T-->C) and 14693 (A-->G) between the two groups (P<0.05). In 4 of 184 cases, a T to C transition at nucleotide position 14693 was uncovered for the first time. The prevalence of 16189 variant among type 2 diabetes was significantly higher that of the controls (36.9% vs 26.6%, P=0.03). Moreover, the type 2 diabetes with 16189 variant showed higher fasting serum insulin level and higher HOMA-IR level than those without 16189 variant; stepwise multiple regression analysis showed the 16189 variant was an independent factor contributing to HOMA-IR (R(2)=0.043, P=0.037). Secondary structure prediction revealed that there were differences in 3394 T-->C vs wild-type ND1 protein and in 14693 A-->G vs wild-type tRNA(Glu) protein.
  
  
  CONCLUSIONS
  The mutations of 3394 (T-->C) and 14693 (A-->G) may contribute to the genetic predisposition to type 2 diabetes; 16189 (T-->C) variant is associated with insulin resistance and risk factor of diabetes.
authors.affiliation: Department of Clinical Laboratory, Zhongnan Hospital, Wuhan University, Wuhan, Hubei, P. R. China.
authors.forename: Dong-ling
authors.initials: DL
authors.lastname: Tang
authors.forename: Xin
authors.initials: X
authors.lastname: Zhou
authors.forename: Ke-yuan
authors.initials: KY
authors.lastname: Zhou
authors.forename: Xia
authors.initials: X
authors.lastname: Li
authors.forename: Lei
authors.initials: L
authors.lastname: Zhao
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.forename: Fang
authors.initials: F
authors.lastname: Zheng
authors.forename: Song-mei
authors.initials: SM
authors.lastname: Liu
mesh_terms: D000368:Aged; D001483:Base Sequence; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000737:chemistry / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length
chemical_list: D004272:DNA, Mitochondrial; D007328:Insulin