Crohn's disease is associated with novel polymorphisms in the 5 '-flankingregion of the tumor necrosis factor gene

Background & Aims: Tumor necrosis factor (TNF) is considered to play an imp ortant role in the pathogenesis of Crohn's disease (CD). Recently, 3 polymo rphisms in the 5'-flanking region of the TNF gene at positions -1031, -863, and -857, which are related to high transcriptional promoter activity, hav e been identified in the Japanese population. In an effort to understand po tential genetic association with CD, we evaluated patients diagnosed with C D and ulcerative colitis (UC) in the presence of other novel polymorphisms. Methods: Blood samples were obtained from 103 patients with CD and 76 pati ents with UC. Polymorphisms in the TNF gene at their respective positions w ere analyzed by direct sequencing, and the allele frequencies were compared with those determined previously in a healthy Japanese population. Results : Allele frequencies of -1031C, -863A, and -857T in normal controls were 16 .0%, 14.0%, and 17.7%, respectively. Polymorphic allele frequencies at posi tions -1031, -863, and -857 were 24.3%, 21.8%, and 27.2% in CD and 11.8%, 1 1.2%, and 11.8% in UC, respectively. The frequencies at all 3 positions wer e significantly higher in CD patients than in UC patients or healthy contro ls. Among the subgroups of CD, small bowel disease showed the highest frequ encies. Conclusions: Although the findings need to be confirmed in other po pulations with larger numbers of patients, TNF gene polymorphisms -1031C, - 863A, and -857T are positively associated with CD; they may influence not o nly the susceptibility to CD but also the disease location.