Differences in spontaneous allograft acceptance after liver transplantation among inbred rat strains might be explained by variation in the local production of TNF-α as a potent mediator of the inflammatory response. In this study, we hypothesize that nucleotide differences in the rat Tnf gene influence TNF-α protein expression. As such, polymorphisms in the Tnf gene may also provide a possible explanation for differences in survival of allogeneic liver grafts among inbred rat strains. We therefore investigated the capacity of mononuclear cells to produce TNF-α in response to a mitogenic stimulus and the Tnf locus was sequenced in six different inbred rat strains. Among the six strains (AUG, BN, DA, LEW, PVG and WF), 44 nucleotide differences including 36 single nucleotide polymorphisms (SNPs), five simple sequence length polymorphisms, two deletions and one insertion, were found in the Tnf gene. Although, the inbred rat strains differed significantly in mean levels of maximum TNF-α production (P = 0.001), no associations were found with nucleotide differences within the Tnf gene. In conclusion, our results indicate that differential in vitro TNF-α responses among inbred rat strains are not associated with nucleotide differences within non-coding regulatory regions of the rat TNF-α gene. Without an established relationship between polymorphisms and expression of the TNF-α gene, it is preliminary to address a possible association of Tnf gene polymorphisms with rat liver allograft survival.

Gene polymorphisms, Inbred rat strains, Liver transplantation, TNF-α
dx.doi.org/10.1016/j.trim.2005.04.002, hdl.handle.net/1765/62344
Transplant Immunology
Department of Surgery

Warlé, M.C, van der Laan, L.J.W, Kusters, J.G, Pot, R.G, Hop, W.C.J, Segeren, K.C.A, … Tilanus, H.W. (2005). No association between tumor necrosis factor-α production and gene polymorphisms among inbred rat strains. Transplant Immunology, 14(2), 77–82. doi:10.1016/j.trim.2005.04.002