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The Study Of Association Between Tumor Necrosis Factor Alpha Genetic Polymorphism And Inflammatory Bowel Disease

Posted on:2005-09-16Degree:MasterType:Thesis
Country:ChinaCandidate:L J XiangFull Text:PDF
GTID:2144360122981174Subject:Internal Medicine
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Background and objectiveInflammatory bowel disease(IBD) as an autoimmune disease is a chronic inflammatory disease of the gastrointestinal tract which involves an immune-mediated inflammatory process including ulcerative colitis (UC) and Crohn's disease (CD) .Though the pathogenesis for IBD remains unknown, it was studied extensively in aspects of immunity , inheritance and etiology . Some clinical evidence such as clustering within families showed the greatest risk factor of genetic susceptibility and a polygenic mode of inheritance. When hunting for genetic risk factors leading to IBD , HLA gene , TNF-a geneticpolymorphism in the promoter region are included. In China reports on relation between the TNF-a genetic polymorphisms and IBD are rare. The aim of the study was to investigate the effect of the prevalence of the tumor necrosis factor alpha (TNF-a) promoter polymorphisms at position -308 on the susceptibility and phenotypic expression of IBD in Chinese people, and the relation between the distribution of -308 TNF-a genotypes and serum C-reactive protein (CRP) and clinical activity index (CAI) in order to study the association between the polymorphism and activity or severity of IBD, Subjects and methods 1. SubjectsAccording to the diagnostic criteria agreed at the meeting about inflammatory bowel disease in ChenDu in 2000,a group of IBD admitted to The First Affiliated Hospital of ZheJiang University School Of Medicine and Sir Run Run Shaw Hospital of zhejiang University School of Medicine diagnosed by clinic, radiology, endoscope, pathology, from 2003.7 to 2004.4, were investigated. It consisted of 32 of UCand 20 of CD, in UC group ,it had 22 males and 10 females with a median age of 43.8 years(range 18-63);in CD group , it had 10 males and 10 females with a median age of 38.6 years(range 14-78) . another was control group ,it had 30 people consisted of 18 males and 12 females with a mean age of 38.6 years(rang 22-56 years),all people with no relationship coming from ShangYu People's Hospital were healthy in medical examination.2. MethodsMethod of study: The TNF-alpha genetic polymorphisms at position -308 were determined by the Polymerase Chain Reaction Restriction Fragment Length Polymorphism (PCR-RFLP) method. Serum C-reactive protein in UC and CD were measured by nephelometry. CAI includes UCAI and CDAI, UCAI and CDAI were assessed by the Lichtiger and the Harvey Bradshaw Index (simplified CDAI) respectively, UCAI 10 and CDAI 5 were described as more activity of diseasesStatistical analysis: the statistical significance of any difference in frequency of each polymorphic genotype between the patients and the controls and between distribution of eachpolymorphic genotype and CAI were evaluated by the Chi-squared test, P values were calculated using Fisher' exact test probability .The Wilconxon-signed rank sum test was used to compare the values of the CRP levels between the groups of TNF1 genotype and TNF2 genotype.P<0.05 was considered statistically significant.Analysis was completed by SPSS12.0. Results and discussionThe frequencies of the genotype at position -308 were as follows : in UC group there were 20 of TNF1/1 genotype(20/32,62.5%), 11 of TNF1/2 genotype(ll/32,34.4%), 1 of TNF2/2 genotype(l/32,3.1%); in CD group there were 13 of TNF1/1 genotype(13/20,65.0%), 7 of TNF1/2genotype(7/20,35.0%), Oof TNF2/2 genotype(0/20,0.0%); and in control group there were 19 of TNF1/1 genotype(19/30,63.4%), 10 of TNF1/2 genotype(10/30,33.3%), 1 of TNF2/2 genotype(l/30,3.3%).There were no significant difference in distribution of TNFK TNF2 genotype between the controls and UC. CD(P>0.05).The mean level of CRP in IBD patients with TNF1 genotype as 1 1.47 6.02mg/L,lower than 21.40 10.56mg/Lin patients with TNF2 genotype (P<0.05) .In patients with TNF2, there were 5 of 7 with CDAI 5 and 9 of 12 UCAI 10, more than 2 of 13 and 6 of 20 with TNF2 (P<0.05).Tumor necrosis factor alpha (TNF-a) is a pro-inflammatory cytokine that acts as a potent immune media...
Keywords/Search Tags:inflammatory bowel disease, TNF-α-308, polymorphism, susceptibility, activity
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