Research On Genetics Of Familial Diabetes In Yunnan Han Population DNA3243,3316,3394,3714 Mitochondrial Mutation Sites

Part I Metabolic status in Diabetes Families in Yunnan Province[Objective] To understand the Clinical features and the metabolic status in type2diabetes mellitus families in Yunnan province. And compare the difference between familial and non-familial type2diabetic population.[Methods] Record general and detection of blood glucose, blood lipids, HbAlc, lactic acid, insulin-C peptide, true insulin and proinsulin in203cases Familial type2diabetes.192cases of non-kinship in patients with type2diabetes and175healthy controls.Calculate the HOMA-IR, ISI, and HOMA-β. And compare these indicators in the three groups.[Results]There was a significant difference between the experimental group and NC group in AGE、SBP、WHR、FPG、PPG、HBA1C、DBP、BMI、HDL-C、FINS、PINS、ISI、HOMA-IR、 PI、TI、FCP、PCP、HOMA-3、And there was a significant difference between the experimental group and T2DM group in PPG、ISI、HDL-C、FINS、PINS、HbAlc、HOMA-IR、PI、TI、 LDL-C.[Conclusion](1) No significant difference in age, blood pressure, BMI, WHR and lactic acid between familial and non-familial type2diabetic population.(2) A family history of diabetes insulin resistance index was lower than patients with no family history of diabetes. But the insulin sensitivity index were higher than those non-familial type2diabetic population.(3) Have a family history of diabetes PI and TI lower than non-familial type2diabetic population..(4) TI is an independent risk factor of family history of diabetes, HDL-C is an independent protective factor of family history of diabetes. Part Ⅱ Study on genetics between point mutations of mitochondrial gene and diabetes in Yunnan.[Objective] To explore the distribution and clinical features of various mitochondrial(mt)DNA tRNA Leu(UUR) and ND1gene mutations among Chinese in Yunnan Province. In order to find new pathogenic sites in MDM.[Methods] PCR restriction fragment length polymorphism (PCR-RFLP) analysis was used to screen point mutations of mtDNA (3243,3316,3394,3714) in203cases Familial type2diabetes,192cases of non-kinship in patients with type2diabetes and175healthy controls f followed by direct sequencing to confirm mutation。[Results] There were2carriers (1%) of3316G�'A mutation,4carriers (2%) of3394T�'C mutation in the experimental group; There were5carriers(2.6%) of3316G�'Amutation,4carriers (2.1%) of3394T�'C mutation,2carriers (1%) of3714A�'G mutation in the T2DM group; There were4carriers (2.3%) of3316G�'Amutation,3carriers (1.7%) of3394T�'C mutation in the normal glucose tolerance group. Each mutation point sequencing results are consistent with the PCR-RFLP pattems.Each locus mutation rate in each group differences among groups were not statistically significant (P>0.05).[Conclusion] It’s shown that the frequency of mtDNA tRNALeu(UUR) A3243G mutation is fairly low in patients with T2DM in Yunnan area. Mitochondrial ND1gene with3316G�'A,3394T�'C mutations is non-pathogenic gene mutations;3714A�'G mutations is Nonsense mutation Part III Study on genetics between point mutations of mitochondrial gene and diabetes in Yunnan families.[Objective] To explore the distribution, the genetic pattern and the clinical features of Mitochondrial DNA mutation sites in Diabetic pedigrees.[Methods] PCR restriction fragment length polymorphism (PCR-RFLP) analysis was used to screen point mutations of mtDNA (3243,3316,3394) in22families of176people, followed by direct sequencing to confirm mutation。[Results] In the22families. There were6carriers of3316G�'A mutation in the No.33families. There were6carriers of3394T�'C mutation in the No.36families. did not find other mutations families and mtDNA tRNALeu(UUR) A3243G mutation.[Conclusion]①In NGT group, compared with no mutations, people has mitochondrial ND1gene with3316G�'A mutation age, HOMA-beta, lactic acid, FINS, HOMA-IR, FCP were higher. and ISI lower. Mitochondrial ND1gene with3316G�'A mutation is non-pathogenic gene mutations;②In NGT group, compared with no mutations, people has mitochondrial ND1gene with3394T�'C mutation lactic acid and triglyceride were higher.③The point mutation of T3394C in ND1gene could be related to the occurrence of T2DM in No.36families. And the mutation may be induced diabetes in the synergistic effect of other risk factors.③The closer genetic relationship with the proband, the lower the insulin sensitivity index and the higher the insulin resistance index in pedigree of mtND13394T�'C mutation. And female NGT members of FINS, HOMA-IR, TI, HbA1C were higher than male NGT members in the same family, but ISI is lower than those male NGT members.⑤mtND13394T�'C mutations may exist in mainly maternally inherited type2diabetes.