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

Abstract

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). It 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.