The association between cytokine gene polymorphisms and kidney allograft survival

Cytokines regulate cellular and humoral immune responses. One determinant of the variable cytokine production observed among individuals is genetic polymorphism in cytokine genes. These polymorphisms represent normal allelic variations in the cytokine genes; usually single base changes. Homozygous genotypes for high producer alleles are generally associated with high cytokine production, heterozygotes with intermediate production, and homozygotes for the low producer alleles with low cytokine production. Cytokines have been implicated in the regulation of acute and chronic rejection of allografts. The aim of the study was to evaluate the promoter polymorphism of TNF-alpha gene (-308 promoter polymorphism), IL-2 gene (-330 promoter polymorphism), IL-4 gene (-590 promoter polymorphism), and IL-6 gene (-174 promoter polymorphism) in renal transplant recipients with allograft duration under and over 10 years to establish whether aforementioned polymorphism are involved in kidney allogragft survival. The study included 197 renal transplant recipients with well-functioning grafts for 2 to 18 years. The patients were divided into two subgroups: recipients with allograft duration under 10 years and recipent with allograft duration over 10 years. Among renal transplant recipients with allograft duration over 10 years we oberved the prevalence of subjects with the TITI genotype of TNF alpha (low expression of TNF alpha) and GG of IL-6 (high expression of IL-6). There was no difference in relation to IL-2 and IL-4 promoter polymorphism. The resulsts of present study suggest that the TNF-alpha- 308 and the IL-6-174 promoter polymorphisms may be the genetic factors influencing the renal allograft survival.