title: IL18 polymorphism is associated with an increased risk of Crohn's disease.
abstract: BACKGROUND
  The etiology of inflammatory bowel disease, which includes ulcerative colitis and Crohn's disease, has not yet been made clear. However, inflammatory bowel disease is recognized as a multifactorial disease, and innate genetic factors might contribute to the pathogenesis. Cytokine genes are thought to be important in inflammatory bowel disease. Recently, interleukin 18, cloned as a novel proinflammatory cytokine, has been implicated in inflammatory bowel disease, especially Crohn's disease.
  
  
  METHODS
  To identify germline mutations in patients with inflammatory bowel disease, the entire coding region of IL18 was examined using a DNA sequencing procedure.
  
  
  RESULTS
  No functional mutations were found, but a novel single nucleotide polymorphism (SNP) was identified as TCA/TCC at codon 35. In patients with Crohn's disease, the frequency of TCC allele carriers was significantly higher than in healthy controls (chi2 = 9.35, P = 0.002229, OR = 2.58, 95% CI = 1.39-4.80). Also, the magnitude of the association was more remarkable in females (chi2 = 16.36, P = 0.000052, OR = 8.17, 95% CI = 2.73-24.41). The TCC allele at codon 35 of IL18 may increase the risk for Crohn's disease, especially in females.
  
  
  CONCLUSIONS
  IL18 is probably one of several genes that determine susceptibility to Crohn's disease.
authors.affiliation: Laboratory of Hereditary Tumor, Institute for Advanced Medical Sciences, Hyogo College of Medicine, 1-1, Mukogawa-cho, Nishinomiya 663-8501, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Tamura
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Fukuda
authors.forename: Hiroko
authors.initials: H
authors.lastname: Sashio
authors.forename: Naohisa
authors.initials: N
authors.lastname: Takeda
authors.forename: Hiroko
authors.initials: H
authors.lastname: Bamba
authors.forename: Tadashi
authors.initials: T
authors.lastname: Kosaka
authors.forename: Shin
authors.initials: S
authors.lastname: Fukui
authors.forename: Koji
authors.initials: K
authors.lastname: Sawada
authors.forename: Kazutami
authors.initials: K
authors.lastname: Tamura
authors.forename: Masamichi
authors.initials: M
authors.lastname: Satomi
authors.forename: Takahiro
authors.initials: T
authors.lastname: Yamada
authors.forename: Takehira
authors.initials: T
authors.lastname: Yamamura
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Furuyama
authors.forename: Haruki
authors.initials: H
authors.lastname: Okamura
authors.forename: Takashi
authors.initials: T
authors.lastname: Shimoyama
mesh_terms: D000293:Adolescent; D000328:Adult; D017677:Age Distribution; D000368:Aged; D001483:Base Sequence; D016022:Case-Control Studies; D003093:Colitis, Ulcerative / Q000453:epidemiology / Q000235:genetics*; D016001:Confidence Intervals; D003424:Crohn Disease / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015994:Incidence; D020382:Interleukin-18 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D016017:Odds Ratio; D016133:Polymerase Chain Reaction / Q000379:methods; D011110:Polymorphism, Genetic; D011336:Probability; D012016:Reference Values; D018570:Risk Assessment; D012494:Sampling Studies; D012680:Sensitivity and Specificity; D017678:Sex Distribution
chemical_list: D020382:Interleukin-18