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CRP Expression And Analysis Of HLA-DRB1, HLA-DRB1*04 Gene Polymorphisms In Type 2 Diabetics With Or Without Macrovascular Complication

Posted on:2005-12-18Degree:DoctorType:Dissertation
Country:ChinaCandidate:W H WuFull Text:PDF
GTID:1104360122990933Subject:Internal Medicine
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CRP Expression and Analysis of HLA-DRB1 ,HLA-DRB1 * 04Gene Polymorphisms In Type 2 Diabetics with or withoutMacrovascular ComplicationObjectivesTo study the possible role of C-Reactive Protein ( CRP) in the pathogenesis of type 2 diabetes mellitus (T2DM) and its macrovascular complication, the gene polymorphisms of HLA-DRB1 and HLA-DRB1 * 04 alleles in type 2 diabetics with macrovascular complication. To explore the association between inflammation markers and T2DM or it's macrovascular complication. Attempt to find associated gene with T2DM macrovascular complication.C-reactive protein (CRP) is an acute-phase protein that reflects the degree of inflammation. There is now much interest in CRP because there is a growing body of evidence that inflammation plays a major role in the initiation and progression of arteriosclerosis. Since T2DM and arteriosclerosis have common antecedents, we proposed that inflammation plays a role in pathogenesis of T2DM and its macrovascular complication in Chinese. In order to prove this hypothesis , we compared the levels of CRP in participants who had T2DM with or without macrovascular complication, with those in healthy controls and those in participants with non-diabetic macrovascular disease.T2DM is a disease that seriously affects human health. Macrovascular complications of T2DM, pathologically similar to arteriosclerosis, form the leading cause of mortality among such patients and are expected to remain so for the foreseeable future. There is a growing body of evidence that inflammation and immunology plays a major role in the initiation and progression of arteriosclerosis. Since T2DM and arteriosclerotie cardiovascular disease share many antecedent factors that frequently coexist, we designed the present study to investigate whether low-grade inflammation, as measured by CRP, or some HLA specific gene underlies the development of T2DM as well as arteriosclerosis. We alsowant to find some protective gene correlated with T2DM macro vascular complication.Material and methodsAll participants in this study were divided into six groups: healthy controls , IFG individuals ( Group B) , 1GT individuals, T2DM patients without macro-vascular complications, T2DM patients with macrovascular complications , and patients suffering from other macrovascular diseases without DM . Control group were recruited from among blood donors at the Harbin Hematopathy Research Institute ; other research subjects were recruited from the outpatient and inpatient departments of Harbin Medical University.Macrovascular complications included coronary heart disease, cerebral infarctions , and atherosclerosis of the lower limb. Coronary heart disease was confirmed by coronary arteriography, cerebral infarctions were confirmed by computed tomography (CT) or magnetic resonance imaging (MRI) , and atherosclerosis of the lower limb was confirmed by arterial ultrasonic Doppler techniques.Indexes associated with arteriosclerosis and DM that could confound the relation between glucose change and markers of inflammation were detected. These included blood pressure, blood lipid, body mass index ( BMI) , waist-hip ratio ( WHR) , and smoking history. The patients having blood pressure over 140/90 mmHg were diagnosed as hypertensive ones.The determination of CRP levels in type 2 diabetics with or without macro-vascular complication, non-DM patients presenting with macrovascular disease, IFG or IGT patients and normal controls was made by ELISA assay. HLA-DRB1 alleles in 88 type 2 diabetics, including 52 without complication and 36 with macrovascular complication, were examined by PCR-SSP(Polymerase Chain Reaction-Sequence Specific primers). Then detect the HLA-DRB1 * 04 alleles in those patients with special positive DRB1 * 04 lanes.CRP was determined by enzyme-linked immunosorbent assay ( ELISA). The DSL-1042100 ACTIVE?CRP ELISA kit was purchased from Diagnostic Systems Laboratories, Inc. , Webster, Texas, USA. All specimens were storedat -20C until assayed. Sta...
Keywords/Search Tags:C-reactive protein, HLA-DRB1, HLA-DRB1*04, IFG, IGT, T2DM, macrovascular complication
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