The Met196Arg Variation of human TNFR2 confers increased apoptotic signaling and impaired TNF-alpha responses: implication for inflammatory bowel disease

Background & Aims: Tumor necrosis factor-a (TNF-a)-induced signalling is pivotally involved in the pathogenesis of human chronic inflammatory bowel disease (IBD). Selective upregulation of TNF receptor 2 (TNFR2) in colonic epithelial cells has been described to play an important role in epithelial migration (Corredor et al., 2003) and colonic inflammation-associated alteration in the intestinal epithelium (Mizoguchi et al., 2002). A polymorphism in the TNF receptor 2 (TNFR2) gene resulting in an inversion from methionine (TNFR2196MET) to arginine (TNFR2196ARG) at the amino acid 196 has been genetically associate…