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.
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.
Ozeki
Takeshi
T
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.
Furuya
Yoko
Y
Nagano
Chieko
C
Matsui
Chika
C
Takayanagi
Risa
R
Yokoyama
Haruko
H
Yamada
Yasuhiko
Y
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*
D000911:Antibodies, Monoclonal; D008233:Lymphotoxin-alpha; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab