title: Crohn's disease is associated with novel polymorphisms in the 5'-flanking region of the tumor necrosis factor gene.
abstract: OBJECTIVE
  Tumor necrosis factor (TNF) is considered to play an important role in the pathogenesis of Crohn's disease (CD). Recently, 3 polymorphisms in the 5'-flanking region of the TNF gene at positions -1031, -863, and -857, which are related to high transcriptional promoter activity, have been identified in the Japanese population. In an effort to understand potential genetic association with CD, we evaluated patients diagnosed with CD and ulcerative colitis (UC) in the presence of other novel polymorphisms.
  
  
  METHODS
  Blood samples were obtained from 103 patients with CD and 76 patients with UC. Polymorphisms in the TNF gene at their respective positions were 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 positions -1031, -863, and -857 were 24.3%, 21.8%, and 27.2% in CD and 11.8%, 11.2%, and 11.8% in UC, respectively. The frequencies at all 3 positions were significantly higher in CD patients than in UC patients or healthy controls. Among the subgroups of CD, small bowel disease showed the highest frequencies.
  
  
  CONCLUSIONS
  Although the findings need to be confirmed in other populations with larger numbers of patients, TNF gene polymorphisms -1031C, -863A, and -857T are positively associated with CD; they may influence not only the susceptibility to CD but also the disease location.
authors.affiliation: Third Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Negoro
authors.forename: Y
authors.initials: Y
authors.lastname: Kinouchi
authors.forename: N
authors.initials: N
authors.lastname: Hiwatashi
authors.forename: S
authors.initials: S
authors.lastname: Takahashi
authors.forename: S
authors.initials: S
authors.lastname: Takagi
authors.forename: J
authors.initials: J
authors.lastname: Satoh
authors.forename: T
authors.initials: T
authors.lastname: Shimosegawa
authors.forename: T
authors.initials: T
authors.lastname: Toyota
mesh_terms: D000328:Adult; D000483:Alleles; D044466:Asian People / Q000235:genetics; D003093:Colitis, Ulcerative / Q000235:genetics; D003424:Crohn Disease / Q000145:classification / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007564:Japan; D008297:Male; D011110:Polymorphism, Genetic / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D014409:Tumor Necrosis Factor-alpha