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The Relationship Between Polymorphisms Of PAI-1 Gene,PAI-1 Antigenin Plasma With Diabets Nephropathy

Posted on:2005-01-29Degree:MasterType:Thesis
Country:ChinaCandidate:L WangFull Text:PDF
GTID:2144360125950797Subject:Internal Medicine
Abstract/Summary:PDF Full Text Request
Diabetes Mellitus (DM) and its chronic complicating diseases have become the main danger disease. Diabetic nephropathy is one of the most critical chronic complication. The pathogenesis of Diabetic nephropathy is not definitively established. It is associated not only with some conventional danger factors, such as hyperglycemia, hypertension, obesity, Coronary heart disease, smoking habits, but also with alterations in plasminogen activator system and fibrinolysis, genetic predisposition, ethnic factor, et al. Plasminogen activator inhibitor type-1 (PAI-1) plays a primary regulatory role in the plasminogen activator system (Pas), and is the rapid and special physiologic inhibitor of plasminogen activation in blood. PAI-1 is a single-chain glycoprotein with a molecular weight of 52000 Da and consists of 379 amino acids. Its main physiological function is rapidly neutralized endogenous tissue plasminogen activator (t-PA), which binds to t-PA and forms a stable 1:1 complex, Protect Glomerular basement membrane from degradation by enzyom come from blood plasma. Keep tissues structure integrity, Suppress protein degradation during the process of connective tissue variation, clitting, complement activation, inflammatory reaction, and so on. In cell cycle, the changes of PAI-1 transcription and accumulate at innercell has importance value to keep cell normal function. Following the course progress of type 2 Diabetic Nephropathy, Elevated PAI-1 level has been observed in renal local .In case of elevated PAI-1 level, the action of fibrinolysis is depressed, which contributes to the fibrous protein deposit and results in exocytic matrix progressive pile up, glomerular basement membrane thicken, Glomerulosclerosis. Hence, Impaired fibrinolysis may play a crucial role in diabetic microangiopathy, So, elevated PAI-1 level may as a risk factor for Diabetic Nephropathy, is involved in the development and the clinical course of Diabetic Nephropathy. PAI-1, as a key inhibitor in fibrinolysis system, which plasma levels and activity are not only depend on the gene regulation but also related on the metabolic determinants such as BMI, TG, FPI. Polymorphism in the PAI-1 gene promoter, a single guanosine insertion/deletion variation, has been shown to be related to on the one hand is elevated PAI-1 plasma levels, on the other hand is Diabetic Nephropathy predispose. Study of relationship between PAI-1 gene polymorphisms and Diabetic Nephropathy in Chinese diabetic patients has not been reported up to now. In order to investigate the relationship between the gene polymorphism of PAI-1 with the Diabetic Mellitus and Diabetic Nephropathy in the northern part of the China of han people, we study the genotype at a single nucleotide insertion/deletion (4G/5G) polymorphism in the promoter region of the PAI-1 gene,circulating PAI-1 levels,and some metabolic parameters such as BMI,TG,HbA1c,FPI and so on in normal person, in type 2 diabetes with and without nephrosis, so that bring to light the coherence of associatite. Methods: 114 examinees of type 2 Diabetic Mellitus in our endocrine department ward were divided into two groups; the group A consist of 38 simple Diabetic Mellitus, the group B include 76 Diabetic Nephropathys, according to the Urine albumin excretory rate (UAER), all patients with UAER 20~200μg/min were devided into B1 group, others were in B2 group. And 32 nephrosis patients,30 healthy controls were also choosen. All examinees were measured body height, weight, TG, TC, HbA1c and plasma insulin levels on an empty stomach in the morning. The results shows 1. The levels of plasma PAI-1 antigen,HbA1C,TG in diabetic patients were obviously higher than that in healthy controls or nephrosis patients, Diabetic Nephropathy group's were significantly higher than that in the others groups'( p<0.05). 2. The 4G/5G polymorphism in the PAI-1 gene promoter region could influence the levels of plasma PAI-1 antigen. The patients with homozygous for the 4G alleles had the signifi...
Keywords/Search Tags:Type 2 Diabetes, Diabetic nephropathy, Gene, Polymorphism, Plasminogen activator inhibitor-1
PDF Full Text Request
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