[The role of cytokine gene polymorphisms in organ and haematopoietic stem cell transplantation]

Abstract

The development of molecular biological techniques during the last decade has led to the recognition of a series of polymorphic sites in the regulatory regions of cytokine-encoding genes. Different alleles are associated with the binding of transcriptional factors and various degrees of cytokine production. Therefore each person has an individual profile of high and low cytokine responses. Some individuals are more susceptible to inflammatory conditions and the development of an immune response after transplantation. It has been documented that in heart transplantation high TNF-alpha/low IL-10 producers had high levels of graft rejection, while in renal transplants high TNF- alpha /high IL-10 producers were characterized with worse prognosis. The polymorphic features of genes encoding cytokines also associate with the outcome of bone marrow transplantation. It was shown that recipient TNFd, IFN- gamma (CA) and IL-10(-1064) microsatellite polymorphisms and IL-10 (-1082) and IL-6 (-174) SNP polymorphisms are associated with acute GvHD manifestation. No relation was found between TNFA (-308) and aGvHD. Recently, the influence of donor polymorphism within the IL-10 and IL-6 genes was documented. Polymorphism of the TNFd, TNFA (-308), TNFA (-238), TNFB (-252), and IFN- gamma (+874) genes in donors were not related to this complication. In addition, donor and recipient IL-6 gene polymorphism and recipient IFN- gamma and IL-10 alleles were described as risk factors of cGvHD.