| Inflammatory bowel disease (IBD) is currently classified as ulcerative colitis (UC) or Crohn's disease (CD) on he basis of clinical, radiological and histological criteria. While the aetio-pathogenesis of IBD is unknown, the effpeople all agree that IBD is chronic inflammatory disorders of the intestines characterized by a dysregulated mucosal immune response, increasing evidence suggests that it is likely to be caused by combination of environmental factors at work in a genetically susceptible host. A a number of lines of epidemiological evidence support a role for genetics in determining IBD susceptibility. Recent research has focused on the role that genes may play in determining the clinical phenotype of disease in addition to susceptibility. If the hypothesis is right, then we can determine clinical phenotype lies in defining accurately different clinical subtypes according to the genotype. If it proves possible to define genes which determine clinical phenotype then we may be able give patients an accurate assessment of their prognosis at the time of diagnosis. UC and CD are chronic diseases that affect young adults just at the time when they may be going through education or making important life choices, and this may be very helpful in their overall management. We may be able to predict which patients might develop extra-intestinal manifestations, which patients will relapse most often and so benefit most from maintenance treatment, and which patients will be likely to require surgery. If we are able to predict which patients may be at greatest risk of developing UC associated cancer, then we might target screening procedures more efficiently.To study the relationship of genes and IBD patients in Chinese Han population, this thesis performed a two-stage study.Previous studies have shown NOD2/CARD15 gene is the first susceptibility gene toCrohn's disease, three single nucleotide polymorphisms(SNPs) of the gene have been identified to be associated with Crohn's disease in the Caucasians, but not in the Japanese. So we have evaluated the N0D2/CARD gene polymorphisms in Chinese patients to determine whether the gene is associated with susceptibility to CD in Chinese Han population. Blood samples were obtained from 32 paients with CD, 110 patients with ulcerative colitis, and 292 healthy controls in Zhejiang location. None of the patients with CD had heterozygous or homozygous common SNP variants, but we first found other two rare SNP variants in Exon 4. It suggested that NOD2 gene may be still play an important role in the pathogenesis of CD in Chinese Han population.Recent association studies have evaluated the role of TNF promoter polymorphisms in Caucasian populations but data have been inconsistent. Interpretation of these data is limited by the complex patterns of LD across this region and the lack of reliable techniques to study the functional effects of specific promoter polymorphisms. Trans-racial mapping in an ethnically distinct but homogenous population may help clarify these associations. To investigate the association between TNF promoter polymorphisms and susceptibility to UC in the Chinese Han population. We studied 110 unrelated UC patients and 292 healthy controls from Zhejiang location. Genotyping for 6 common TNF promoter polymorphisms was carried out using polymerase chain sequence-specific primer (PCR-SSP). We found TNF-308A was associated with disease. We report the first association study of TNF promoter polymorphisms in Chinese patients with ulcerative colitis. We also studied the relation ship between Chinese UC patients and another good candidate gene—NKG2D, but got negative result.This thesis also support a role for genetics in determining Chinese IBD susceptibility, further mapping of this gene-dense region in a larger cohort of Chinese Han population is now required. |
PDF Full Text Request