TNF-α, TGF-β, IL-10, IL-6, and INF-γ alleles among African Americans and Cuban Americans. Report of the ASHI minority workshops: Part IV

Abstract

Point mutations or single nucleotide substitutions in the regulatory regions of cytokine genes may affect levels of cytokine expression and have been associated with acute and chronic rejection in organ transplantation, severity of graft-versus-host disease in hematopoietic stem cell transplants, and predisposition to autoimmune disorders. Because these cytokine variants have been studied primarily among Caucasians, we defined the alleles and frequencies of five cytokines among 691 unrelated, adult African Americans and 296 Cuban Americans in the American Society for Histocompatibility/National Institutes of Health Minority HLA Workshops. The genotypes of all cytokines, except for transforming growth factor (TGF)-β among African Americans, were found to be in Hardy-Weinberg’s equilibrium. Genotype frequencies among African American and Cuban American participants were compared with those of 75 North American Caucasian bone marrow donors and with published frequencies. Significant differences were observed in all comparisons except between Cuban and Caucasian Americans for alleles of interferon (IFN)-γ, interleukin (IL)-6, and IL-10. The most notable differences were in genotype frequencies of African Americans compared with those of the two other populations. The frequency of the IFN-γ genotype A/A, which is associated with low expression, was significantly higher in African Americans than in Caucasian or Cuban Americans (0.66 vs 0.37 and 0.26, respectively; p < 0.0001 for both comparisons). The high-expression G/G genotype for IL-6 was more than twice as prevalent among African Americans as among Caucasians and 1.5 times more frequent than among Cuban Americans (respective frequencies: 0.85 vs 0.38 and 0.49; p < 0.0001 for both comparisons). In African Americans, the frequency of the high-expression genotype for IL-10, GCC/GCC, was approximately half that of the frequency in Cuban and Caucasian Americans (0.10 vs 0.19 and 0.23, respectively; p < 0.0001, p = 0.004). Because levels of expression can affect inflammation and immune regulation, differences in cytokine allele frequencies between racial or ethnic groups may contribute to different incidences of autoimmunity and allograft rejection.