title: Analysis of linkage between lymphotoxin alpha haplotype and polymorphisms in 5'-flanking region of tumor necrosis factor alpha gene associated with efficacy of infliximab for Crohn's disease patients.
abstract: Tumor necrosis factor (TNF)alpha is increased in patients with Crohn's disease (CD) and considered to play an important role in the inflammation. Infliximab (IFX) is used as a therapeutic agent for CD. Recently, it was reported that homozygosity for a lymphotoxin alpha (LTA) haplotype (LTA 1-1-1-1) may identify subgroups with a poor response to IFX. In the present study, we characterized the linkage of the LTA haplotype with SNPs in the 5'-flanking region of the TNFalpha gene. In subjects who had homozygosity for each LTA haplotype, 6 nucleotide variations, -857C > T, -522C > G, -357A > C, -261C > G, -159G > T and -96G > T, were found in the 5'-flanking region of the TNFalpha gene. As for linking with the allele, only -857T met the LTA haplotype 1-1-1-1. We concluded that the differences in therapeutic effects of IFX among patients with CD may be explained in part by the induction ability of TNFalpha via the -857C > T polymorphism.
authors.affiliation: Department of Clinical Evaluation of Drug Efficacy, School of Pharmacy, Tokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Ozeki
authors.forename: Yoko
authors.initials: Y
authors.lastname: Furuya
authors.forename: Chieko
authors.initials: C
authors.lastname: Nagano
authors.forename: Chika
authors.initials: C
authors.lastname: Matsui
authors.forename: Risa
authors.initials: R
authors.lastname: Takayanagi
authors.forename: Haruko
authors.initials: H
authors.lastname: Yokoyama
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Yamada
mesh_terms: D024506:5' Flanking Region; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001483:Base Sequence; D003424:Crohn Disease / Q000188:drug therapy / Q000235:genetics*; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D000069285:Infliximab; D008233:Lymphotoxin-alpha / Q000235:genetics*; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D000911:Antibodies, Monoclonal; D008233:Lymphotoxin-alpha; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab