Analysis of linkage between lymphotoxin α haplotype and polymorphisms in 5′-flanking region of tumor necrosis factor α gene associated with efficacy of infliximab for Crohn's disease patients

Tumor necrosis factor (TNF)α 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 α (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 TNFα 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 TNFα 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 TNFα via the −857C > T polymorphism.