Tumour necrosis factor‐α receptor 1 and 2 polymorphisms in inflammatory bowel disease and their association with response to infliximab

Abstract

SUMMARYBackground: The role of tumour necrosis factor-a in the pathogenesis of inflammatory bowel disorders is wellknown and is underscored by the effectiveness of antitumour necrosis factor-a treatment. Tumour necrosis factor-a exerts its effect by binding TNFR1 and TNFR2, which genes map to inflammatory bowel disorders susceptibility loci. Aims and methods: Since TNFR1 and TNFR2 are good candidate genes for inflammatory bowel disorders, we studied the functional TNFR2T587G and the TNFR1A36G mutation in 344 Crohn's disease and 152 ulcerative colitis patients and investigated the relation with disease phenotypes. An association with response to infliximab was evaluated in 166 Crohn's disease patients. Results: The TNFR2 587G allele was more frequent in ulcerative colitis compared with controls (P ¼ 0.03).

TNFα blockade in human diseases: Mechanisms and future directions

“…Treatment with concurrent azathioprine/6-MP was able to overcome these pharmacogenetic predispositions to INF failure. Other genetic polymorphisms, such as polymorphisms in the genes encoding TNF receptors, may predict efficacy to INF [94]. Also helpful would be proteomic and functional genomic studies of peripheral blood, synovial fluid, and synovial tissue obtained from patients undergoing these treatments.…”

Association of IL23R, TNFRSF1A, and HLA-DRB1*0103 allele variants with inflammatory bowel disease phenotypes in the Finnish population

“…Waschke et al 26 reported an association of the TNFRSF1A A36G (P12P) variant with CD. The same variant was negatively associated with stricturing CD phenotype, while Pierik et al 27 reported the association of the same variant with the pancolitis phenotype of UC. The TNFRSF1A gene is localized in the middle of the chr12p13 linkage region that represents 1 of the major peaks in the Finnish whole genome scan.…”

The Met-196 → Arg Variation of Human Tumor Necrosis Factor Receptor 2 (TNFR2) Affects TNF-α-induced Apoptosis by Impaired NF-κB Signaling and Target Gene Expression

“…1A). An association of this variant with an increased susceptibility for chronic inflammatory disorders, such as systemic lupus erythematodes (27,28), human T cell lymphotrophic virus type I-associated myelopathy (29), periodontitis, familial rheumatoid arthritis (30,31), and ulcerative colitis (32), has been reported.…”