Research On Pathogenesis And Coagulation Status In Ulcerative Colitis Patients

Objective:1. To study the role of MDR1C3435T and G2677T/A polymorphism in the pathogenesis and prednisone sensitivity of ulcerative colitis.2. To investigate the PT、 APTT、Fib and D-dimer in UC patients before and after low molecular weight heparin therapy, analyze the coagulation status of UC patients and the treatment effectiveness of low molecular weight heparin therapyMethods:1.86UC patients were divided into three groups according to the history:30newly diagnosed UC patients,30UC patients who were sensitive to the prednisone treatment before and26UC patients on whom the prednisone treatment took no effect. DNA samples were obtained from86UC patients and86healthy subjects (the control group). Genotypes of the MDR1C3435T and G2677T/A loci were determined by polymerase chain reaction of the sequence specific primer (PCR-SSP).2. We divided96UC patients into two groups according to their treatment:49low molecular weight heparin treated UC patients,47UC patients who accepted conventional treatment. We investigated the PT、APTI、Fib and D-dimer in the control group(45healthy persons) and96UC patients before and15days after treatment. All the UC patients were followed-up2months after therapy. We compared those two groups of the therapeutic differences.Results:1. The result of Genotypes of the MDR1C3435T and G2677T/A loci:The genotype frequencies and allele frequencies of all subjects complied well with the Hardy-Weinberg equilibrium.In UC and control groups,to evaluate the difference of CC,CT,and TT, there were significant difference among the two groups(P<0.05); there were also significant difference in C and T allele frequencies(P<0.05). The UC group has a higher frequency of C3435T locus mutation compared with the control group. There was no significant difference of the genotype and allele frequencies of the G2677T/A locus in patients with UC and healthy control (P>0.05). There were significant differences between the newly diagnosed UC patients and prednisone resistant patients in MDR1C3435T locus (P<0.05). The same results occurred in prednisone resistance patients and prednisone sensitive patients (P<0.05). However there was no significant difference in C and T allele frequencies among three groups in MDR1C3435T locus (P>0.05). There was no significant difference of the genotypes and allele frequencies of the G2677T/A locus among three groups (P>0.05)2. The result of determination of PT、APTI、Fib and D-dimer and therapeutic effect in UC patients:The PT and APTT in UC patients before treatment were obviously inferior to healthy controls (P<0.05). The Fib and D-dimer in UC patients before treatment were higher than healthy controls (P<0.05).47UC patients who accepted mesalazine and prednisone therapy was the conventional treatment group, and49UC patients who accepted mesalazine、prednisone and low molecular weight heparin treatment. The treatment course was15days. For49low molecular weight heparin treated UC patients, the PT and APTT were higher than them before treatment (P<0.05), and the Fib and D-dimer were lower than them before treatment (P<0.05). There was no significant difference of PT、APTT、Fib and D-dimer in47UC patients before and after conventional treatment (P>0.05). All the UC patients were followed-up2months after therapy. We determined UC patients’therapeutic effect according to their clinical symptoms and auxiliary examination results. The treatment effectiveness of low molecular weight heparin therapy group was obviously higher than that of conventional treatment group.Conclusion:MDR1C3435T gene mutations increased the risk of UC, and the allelic mutant patients more prone to prednisone resistance. Severe UC patients had high blood coagulation state. High blood coagulation state and (or) intestinal micro thrombosis may be one of the pathogenesis of UC. With the traditional treatment combined with low molecular weight heparin could improve the efficacy.