title: Polymorphisms of the TNF gene and the TNF receptor superfamily member 1B gene are associated with susceptibility to ulcerative colitis and Crohn's disease, respectively.
abstract: The importance of tumor necrosis factor (TNF)-alpha and the TNF receptor gene polymorphisms in the etipathogenesis of inflammatory bowel disease (IBD) has not been elucidated. DNA from peripheral blood samples was obtained from 124 patients with Crohn's disease (CD), 106 patients with ulcerative colitis (UC), and 111 unrelated healthy controls. We examined two single nucleotide polymorphisms (SNPs) of the TNF-alpha gene, TNF (-308 G/A and -238 G/A), an SNP of the TNF receptor superfamily member 1A gene, TNFRSF1A(also known as TNFR1), at codon 12 in exon 1 (CCA/CCG), and two SNPs of the 1B gene, TNFRSF1B (also known as TNFR2), (1466 A/G and 1493 C/T). There was a difference in the carrier frequency for haplotype AG (-308 A, -238 G) between UC patients and the controls (OR=4.76, 95% CI=1.53-14.74, P<0.01). We found a significant difference in carrier frequency for haplotype AT (1466 A, 1493 T) of the TNFRSF1B gene between CD patients and the controls (OR=2.13, 95% CI=1.08-4.21, P<0.05). The significance proved to be greater in CD patients with both internal and external fistula (OR=4.8, 95% CI=1.73-13.33, P<0.01), and in those who were poor responders ( n=22) to our treatments, which consisted of nutritional therapy, medical therapy and surgical therapy (OR=9.24, 95% CI=3.37-25.36, P<0.001). This study suggests that one of the genes responsible for UC may be the TNF gene, or an adjacent gene, and that TNFRSF1B gene polymorphisms contribute greatly to the increased onset risk of CD and to the disease behavior.
authors.affiliation: Department of Genetics, Hyogo College of Medicine, 1-1, Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan. sasshi@hyo-med.ac.jp
authors.forename: Hiroko
authors.initials: H
authors.lastname: Sashio
authors.forename: Kazuo
authors.initials: K
authors.lastname: Tamura
authors.forename: Reiko
authors.initials: R
authors.lastname: Ito
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Yamamoto
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: Yoshihiro
authors.initials: Y
authors.lastname: Fukuda
authors.forename: Kazutami
authors.initials: K
authors.lastname: Tamura
authors.forename: Masamichi
authors.initials: M
authors.lastname: Satomi
authors.forename: Takashi
authors.initials: T
authors.lastname: Shimoyama
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Furuyama
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D015703:Antigens, CD / Q000235:genetics; D016022:Case-Control Studies; D002648:Child; D003093:Colitis, Ulcerative / Q000235:genetics* / Q000276:immunology*; D003424:Crohn Disease / Q000235:genetics* / Q000276:immunology*; D005260:Female; D005787:Gene Frequency; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics*; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D015703:Antigens, CD; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; C415902:TNFRSF1B protein, human; D014409:Tumor Necrosis Factor-alpha