Polymorphisms within the genes encoding TNF-alpha and TNF-beta associate with the incidence of post-transplant complications in recipients of allogeneic hematopoietic stem cell transplants
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Hematopoietic stem cell transplantation (HSCT) is a curative treatment of many hematological disorders. Recent studies have shown the associations between polymorphic features of cytokine-encoding genes and the incidence of post-transplant complications in the recipients of allogeneic HSCT. This review focuses on the relationship between the polymorphic patterns of patient genes encoding tumor necrosis factor (TNF)-alpha and TNF-beta and the manifestation of post-transplant complications, acute graft-versus-host disease (aGvHD), generation of toxic lesions, and mortality. Discussed in more detail are the relationships of TNFd microsatellites and polymorphisms within the promoter region of the TNF-alpha-encoding gene (TNFA) in the position (?308) and within the first intron of the TNF-beta-encoding gene (TNFB). It appeared that heterozygosity within the TNFA promoter and the first intron of the TNFB gene increased the susceptibility to severe grades III?IV of toxic complications, while the presence of the TNFd3 homozygous genotype was associated with a higher risk of severe aGvHD and early mortality in patients after allogeneic HSCT. These results imply that donor-recipient genotyping, extended to cytokine loci, may be of prognostic value for transplantation outcome.
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Katarzyna Bogunia-Kubik, Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Rudolfa Weigla 12, 53-114 Wroclaw, Poland