Cytokine polymorphic analyses indicate ethnic differences in the allelic distribution of interleukin-2 and interleukin-6

Background. Polymorphisms in the regulatory regions of cytokine genes affec t protein production and are associated with allograft outcome. Ethnic orig in has been identified as a significant prognostic factor for several immun e-mediated diseases and for outcome after allotransplantation. A clear rela tionship between cytokine polymorphisms and ethnicity has not been shown. Methods. One hundred sixty subjects including 102 whites and 43 African-Ame ricans were studied. Using polymerase chain reaction-based assays and, in s ome cases, restriction enzyme digestion, we determined genetic polymorphism s for the cytokines interleukin (IL)-2, IL-6, IL-10, tumor necrosis factor- alpha, transforming growth factor-beta, and interferon-gamma (IFN-gamma). G enetic polymorphism. frequencies were then compared to ethnicity using chi- square analysis and Fisher's exact two-tailed tests. Results. For both the IL-2 and IL-6 genes, we found that whites and African -Americans differed significantly (P <0.05) in their allelic distribution a nd genotype frequency. A trend toward ethnic distribution was noted among t he alleles and genotypes for the IL-10 and IFN-gamma genes. We found no cor relation between ethnicity and either allelic distribution or genotype freq uency for the tumor necrosis factor-alpha or transforming growth factor-bet a genes. When comparisons were made between patients with or without a hist ory of kidney failure, the allelic or genotypic distributions for the IL-6 and IFN-gamma genes were found to significantly differ. Conclusions. Our work demonstrates a correlation between ethnicity and poly morphisms in several cytokine genes. In addition, we found that patients re quiring renal transplantation differ from the general population with regar d to certain cytokine gene polymorphisms. These findings may have relevance in making prognostic determinations or tailoring immunomodulatory regimens after renal transplantation.