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An Association Study Of MTHFR Gene Polymorphism With LEDVT And The Clinical Study Of New Interventional Therapy For LEDVT

Posted on:2004-02-22Degree:DoctorType:Dissertation
Country:ChinaCandidate:Y B ZhouFull Text:PDF
GTID:1104360092495842Subject:Medical imaging and nuclear medicine
Abstract/Summary:PDF Full Text Request
PurposeDeep venous thrombosis{ DVT) , especially the deep venous thrombosis of lower extremity ( LEDVT) , is a major medical problem with significant morbidity and mortality from its associated complications, such as pulmonary embolism (PE)and post -thrombotic syndrome (PTS). It is essential to explore the risk factors and the therapy for LEDVT and PE.Hyperhomocysteinemia is an established risk factor for DVT and which raising the question of whether the methylenetetrahydrofolate reductase (MTHFR) gene polymorphism is related to DVT, but it's controversial in Whites. There is a racial difference in the risk factor for DVT between Chinese and Whites. Therefore, there is a strong need to identify whether MTHFR gene polymorphism is related to LEDVT in Chinese.Deep venous thrombosis of lower extremity is a common disorder and an important cause of morbidity and mortality. The ideal goals of therapy for it is the elimination of the embolic potential of existing thrombus, restoration of unobstructed flow, prevention of further thrombosis, and preservation of venous valve function. Meeting these goals will not only prevent PE but will also minimize the long - term sequelae of venous hypertension and the development of the PTS. Treatment strategies aimed at eliminating or reducing the risk of PTS should focus on preserving valvular function and eliminating the risk of continued venous obstruction following LEDVT. The standard systemic anticoagulation with hepa-rin followed by warfarin therapy does not promote clot lysis to reduce the thrombus load nor does it contribute to the restoration of venous valvular function. Systemic thrombolytic therapy has had a low thrombolytic efficiency and isfraught with a threefold increase in major bleeding complication rate. Surgical thrombectomy has had limited success rates, with early recurrent thrombosis. More recently, percutaneous aspiration thrombectomy, percutaneous mechanical thrombectomy, transvenous insertion of inferior vena cava( IVC) filter, ballon angioplasty for thrombosis fragmentation and endovascular stent placement are now available to treat LEDVT and PE, but mechanical fragmentation devices, mechanical lysis and aspirating devices and inferior vena cava filter are too expensive to be afforded by Chinese. So it is important to explore new intervention-al therapies and new devices to satisfy the need of Chinese patients with LEDVT.Methods and ResultsExperiment I . Analysis of the Risk Factors of LEDVT and Its Association with MTHFR Gene PolymorphismMethods1. Subjects:This analysis included 73 patients with LEDVT and 109 heathy controls. Patients were consecutive cases diagnosed with ultrasound confirmed.2. Methods:(1) MTHFR Genotyping.Genomic DNA was isolated, using standard methods, from peripheral blood of subjects. The MTHFR genotypes at the C677T and A1298C sites were analyzed by PCR based RFLP methods.(2) Statistical Analysis.Allele frequencies were calculated by gene counting in patients and controls. The Hardy - Wemberg equilibrium was analyzed by the Chi - square test for all the genotypes. Mean age and sex difference were tested by Student t - test and Chi - square test, respectively, Unconditional logistic regression was used to assess the association of MTHFR C677T and A1298C mutation with LEDVT,and odds ratio (OR) and 95% confidence interval (Cl)were calculated.Results1. Nineteen patients have a risk factor for LEDVT (accounting for 26% ). 15 of those have a risk factor of trauma of lower extremity or long term immobilization ( accounting for 78.9% ).2. No statistical differences were observed between cases and controls in the distribution of age ( p = 0. 591) and sex ( p = 0. 882). The allele frequencies for MTHFR 677C and 677T were 37.0% and 63.0% , respectively, among cases, and 61. 0% and 39. 0% , respectively, among controls. These differences were statistically significant ( p < 0. 01). The distribution of MTHFR 677TT, 677TC, 677CC genotypes among controls was 15.6% , 46. 8% ,...
Keywords/Search Tags:Venous thrombosis, MTHFR, Gene polymorphism, Pulmonary embolism, Vena caval filters, Follow-up studies, Radiology, interventional
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