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Study On The Relationship Between MMP-9 Gene Polymorphism And The Vascular Complications Of Type 2 Diabetes

Posted on:2005-03-15Degree:MasterType:Thesis
Country:ChinaCandidate:Y SunFull Text:PDF
GTID:2144360125452501Subject:Endocrine and metabolic diseases
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AbstractThe MMPs constitute a family of endopeptidases that have in common the presence of zinc in their active site, a dependency on Ca2+ for their activity. The MMPs can degrade all kinds of contents of ECM except polyglycan , and contribute to cell proliferation , neovascularogenesis and tissue remodeling and so on , so they participate in the processes of various pathophysiology in vivo . As one of the most important members , the substrates of MMP-9 are the main contents of vascular basement membrane and extracellular matrix , so its expression level and the change of activation have been attached much importance to vascular disease .In recent studies , it has been found that C-1562-T allele gene polymorphism in the promoter region of MMP-9 gene are both associated with the gene transcriptional activation , and its activities have relationships with the vascular complications of T2DM . ObjectiveTo investigate the relationships between C-1562-T allele gene polymorphism and the macro- and micro vascular complications of T2DM in Tianjin. MethodsFasting blood sample of 288 T2DM patients and 120 health controls who were unrelative were collected randomly , the genome DNA was obtained from the leukocytes , and then PCR-RFLP method was performed to investigate the genotype of MMP-9 gene promoter C-1562-T site. Results1. C,T alleles and CC,CT,TT genotypes were found in T2DM subject, but we failed to get TT genotype in normal control group. From the statistic data , we found that there was no difference between type 2 diabetic group and the normal control group in the frequency of the two alleles and the three genotypes .6Abstract2. In the type 2 diabetic group, C allele and CC genotypes of diabetes without macroangiopathy group were significantly increased than those of diabetes with macroangiopathy group; there were the similar tendency in the respective analyses of CHD,ASO and CVD; but there was no statistically differency in CVD group.3. A decreased frequency of T allele was observed in type 2 diabetes with microalbuminuria as compared with T2DM without nephropathy or T2DM with clinical proteinuria; and the frequency of T allele in the latter two groups were similar.4. General analysis of T2DM with nephropathy or macroangiopathy shows that the lowest frequency of T allele and CT,TT genotypes in the group of type 2diabetes simple with nephropathy, the highest frequency in the group of type 2diabetes simple with macroangiopathy and the frequency of those in the group of type 2diabetes with both complications was similar with that of without the two complications. What's more ,TT genotype was found only in the two groups with macroangiopathy.5. T allele frequency was increased gradually in non-DR ,BDR and PDR group groups ,but there were no significant difference.6. Genernal analysis of type 2 diabetes with DN and DR indicates that T allele and CT,TT genotype frequency were the lowest in type 2 diabetes simple with DN group , highest in type 2 diabetes simple with DR group, the frequency of those in the group of type 2diabetes with both complications was similar with that of without the two complications,but the statistical difference was not reached.Conclusionl.C,T allele and CC,CT,TT genotypes frequencies were same in normalAbstractcontrol group and T2DM groups.2. In T2DM group, the frequencies of C allele and CC genotypes were markedly increased in T2DM without macroangiopathy , therefore C allele may be the protective gene of diabetic macroangiopathy(P=0.001).3. T allele and CT,TT genotypes frequencies were significantly decreased in T2DM simple with nephropathy , therefore T allele may be the protective gene of DN(P=0.001).4. T allele and CT,TT genotypes frequencies were increased in T2DM with retinopathy , especially proliferative retinopathy , but there was no statistical difference.5. T2DM and its chronic complications were a kind of complicated syndrome affected by gene and environment factors in vivo and in vitro involving various pathological processes. The char...
Keywords/Search Tags:Matrix metalloproteinases-9, Gene polymorphism, Type 2 diabetes mellitus, Arteriosclerosis, Diabetic nephropathy, Diabetic retinopathy
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