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.
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.
Bogunia-Kubik
Katarzyna
K
Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland. bogunia@iitd.pan.wroc.pl
D016207:Cytokines / Q000235:genetics; D005838:Genotype; D006086:Graft vs Host Disease / Q000235:genetics* / Q000276:immunology*; D006680:HLA Antigens / Q000235:genetics; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects* / Q000401:mortality; D006801:Humans; D008233:Lymphotoxin-alpha / Q000235:genetics*; D018895:Microsatellite Repeats; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D016207:Cytokines; D006680:HLA Antigens; D008233:Lymphotoxin-alpha; D014409:Tumor Necrosis Factor-alpha