title: Association between IL-18 gene promoter polymorphisms and inflammatory bowel disease in a Japanese population.
abstract: BACKGROUND
  Interleukin-18 (IL-18) is a pleiotropic cytokine that induces the production of interferon (IFN)-gamma and also to regulate Th2 cytokines. Recently, association studies between IL-18 gene promoter polymorphisms and several Th1- or Th2-mediated inflammatory diseases were reported. In inflammatory bowel diseases (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), recent evidence suggests that IL-18 is involved in the pathogenesis.
  
  
  METHODS
  Using DNA direct sequencing, we investigated IL-18 gene promoter polymorphisms at -607C/A and -137G/C. Allele, genotype, and haplotype frequencies were determined in 210 Japanese patients with UC, 205 patients with CD, and 212 controls.
  
  
  RESULTS
  In UC, the -137C allele frequency was significantly higher in the proctitis-type patients than in controls (Pc = 0.0068). The -137 genotype frequency was also significantly different in the proctitis-type patients than in controls (Pc = 0.032). No other allele and genotype frequencies were significantly associated with UC after Bonferroni correction. Furthermore, the frequency of haplotype 2 (-607A, -137C), which had a lower promoter activity and IFN-gamma mRNA level than the other haplotypes as previously reported, was significantly higher in the proctitis-type patients than in controls (Pc = 0.01). In CD, we could not find any significant differences.
  
  
  CONCLUSIONS
  IL-18 gene promoter polymorphisms may not be associated with disease susceptibility but related to the extent of disease in UC.
authors.affiliation: Division of Lower Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Takagawa
authors.forename: K
authors.initials: K
authors.lastname: Tamura
authors.forename: N
authors.initials: N
authors.lastname: Takeda
authors.forename: T
authors.initials: T
authors.lastname: Tomita
authors.forename: Y
authors.initials: Y
authors.lastname: Ohda
authors.forename: K
authors.initials: K
authors.lastname: Fukunaga
authors.forename: N
authors.initials: N
authors.lastname: Hida
authors.forename: K
authors.initials: K
authors.lastname: Ohnishi
authors.forename: K
authors.initials: K
authors.lastname: Hori
authors.forename: T
authors.initials: T
authors.lastname: Kosaka
authors.forename: Y
authors.initials: Y
authors.lastname: Fukuda
authors.forename: H
authors.initials: H
authors.lastname: Ikeuchi
authors.forename: T
authors.initials: T
authors.lastname: Yamamura
authors.forename: H
authors.initials: H
authors.lastname: Miwa
authors.forename: T
authors.initials: T
authors.lastname: Matsumoto
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D044466:Asian People; D003093:Colitis, Ulcerative / Q000235:genetics*; D003424:Crohn Disease / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D020382:Interleukin-18 / Q000235:genetics*; D007564:Japan; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*
chemical_list: D020382:Interleukin-18