Combined impact of hepatitis C virus genotype 1 and interleukin-6 and tumor necrosis factor-alpha polymorphisms on serum levels of pro-inflammatory cytokines in Brazilian HCV-infected patients

摘要

We investigated the association between hepatitis C virus (HCV) genotypes and host cytokine gene polymorphisms and serum cytokine levels in patients with chronic hepatitis C. Serum IL-6, TNF-alpha, IL-2, IFN-gamma, IL-4, IL-10, and IL-17A levels were measured in 67 HCV patients (68.2% genotype 1 [G1]) and 47 healthy controls. The HCV patients had higher IL-6, IL-2, IFN-gamma, IL-10, and IL-17A levels than the controls. HCV G1 patients had higher IL-2 and IFN-gamma levels than G2 patients. The -174IL6G>C, -308TNF alpha G>A, and -1082IL10A>G variants were similarly distributed in both groups. However, HCV patients with the -174IL6GC variant had higher IL-2 and IFN-gamma levels than patients with the GG and CC variants. Additionally, HCV patients with the -308TNF alpha GG genotype had higher IL-17A levels than patients with the AG genotype, whereas patients with the -1082IL10GG variant had higher IL-6 levels than patients with the AA and AG variants. A significant proportion of HCV patients had high levels of both IL-2 and IFN-gamma. The subgroup of HCV patients with the G1/IL6CG/TNF alpha GG association displayed the highest proportions of high producers of IL-2 and IFN-gamma whereas the subgroup with the G1/TNF alpha GG profile showed high proportions of high producers of IL-6 and IL-17A. HCV patients with other HCV/cytokine genotype associations showed no particular cytokine profile. Our results suggest that HCV genotype G1 and IL-6 and TNF-alpha polymorphisms have a clinically relevant influence on serum pro-inflammatory cytokine profile (IL-2 and IFN-gamma) in HCV patients. (C) 2014 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.