title: Combined impact of hepatitis C virus genotype 1 and interleukin-6 and tumor necrosis factor-α polymorphisms on serum levels of pro-inflammatory cytokines in Brazilian HCV-infected patients.
abstract: 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-α, IL-2, IFN-γ, 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-γ, IL-10, and IL-17A levels than the controls. HCV G1 patients had higher IL-2 and IFN-γ levels than G2 patients. The -174IL6G>C, -308TNFαG>A, and -1082IL10A>G variants were similarly distributed in both groups. However, HCV patients with the -174IL6GC variant had higher IL-2 and IFN-γ levels than patients with the GG and CC variants. Additionally, HCV patients with the -308TNFαGG 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-γ. The subgroup of HCV patients with the G1/IL6CG/TNFαGG association displayed the highest proportions of high producers of IL-2 and IFN-γ whereas the subgroup with the G1/TNFαGG 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-α polymorphisms have a clinically relevant influence on serum pro-inflammatory cytokine profile (IL-2 and IFN-γ) in HCV patients.
authors.affiliation: Programa de Pós-Graduação em Imunologia Básica e Aplicada, Universidade Federal do Amazonas, 3000, Rodrigo Otávio Av., Manaus, AM, Brazil; Fundação de Hematologia e Hemoterapia do Amazonas - HEMOAM, 3497 Constantino Nery Av., Manaus, AM, Brazil.
authors.forename: Andréa Monteiro
authors.initials: AM
authors.lastname: Tarragô
authors.affiliation: Programa de Pós-Graduação em Imunologia Básica e Aplicada, Universidade Federal do Amazonas, 3000, Rodrigo Otávio Av., Manaus, AM, Brazil; Fundação de Hematologia e Hemoterapia do Amazonas - HEMOAM, 3497 Constantino Nery Av., Manaus, AM, Brazil; Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, 25 Pedro Teixeira Av., Manaus, AM, Brazil.
authors.forename: Allyson Guimarães
authors.initials: AG
authors.lastname: da Costa
authors.affiliation: Fundação de Hematologia e Hemoterapia do Amazonas - HEMOAM, 3497 Constantino Nery Av., Manaus, AM, Brazil; Instituto Leônidas e Maria Deane - FIOCRUZ-Amazônia, 476 Terezina St., Manaus, AM, Brazil.
authors.forename: João Paulo Diniz
authors.initials: JP
authors.lastname: Pimentel
authors.affiliation: Universidade Federal do Pará, 1 Augusto Corrêa, Belém, PA, Brazil.
authors.forename: Samara Tatielle Monteiro
authors.initials: ST
authors.lastname: Gomes
authors.affiliation: Universidade Federal do Pará, 1 Augusto Corrêa, Belém, PA, Brazil.
authors.forename: Felipe Bonfim
authors.initials: FB
authors.lastname: Freitas
authors.affiliation: Programa de Pós-Graduação em Imunologia Básica e Aplicada, Universidade Federal do Amazonas, 3000, Rodrigo Otávio Av., Manaus, AM, Brazil.
authors.forename: Pritesh
authors.initials: P
authors.lastname: Lalwani
authors.affiliation: Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, 25 Pedro Teixeira Av., Manaus, AM, Brazil.
authors.forename: Ana Ruth S
authors.initials: AR
authors.lastname: de Araújo
authors.affiliation: Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, 25 Pedro Teixeira Av., Manaus, AM, Brazil.
authors.forename: Flamir da Silva
authors.initials: Fda S
authors.lastname: Victória
authors.affiliation: Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, 25 Pedro Teixeira Av., Manaus, AM, Brazil.
authors.forename: Marilú Barbieri
authors.initials: MB
authors.lastname: Victória
authors.affiliation: Universidade Federal do Pará, 1 Augusto Corrêa, Belém, PA, Brazil.
authors.forename: Antônio Carlos Rosário
authors.initials: AC
authors.lastname: Vallinoto
authors.affiliation: Programa de Pós-Graduação em Imunologia Básica e Aplicada, Universidade Federal do Amazonas, 3000, Rodrigo Otávio Av., Manaus, AM, Brazil; Instituto Nacional de Pesquisas da Amazônia - INPA, 2936 André Araújo Av., Manaus, AM, Brazil.
authors.forename: Aya
authors.initials: A
authors.lastname: Sadahiro
authors.affiliation: Centro de Pesquisas René Rachou - FIOCRUZ-Minas, 1715 Augusto de Lima Av., Belo Horizonte, MG, Brazil.
authors.forename: Andréa
authors.initials: A
authors.lastname: Teixeira-Carvalho
authors.affiliation: Centro de Pesquisas René Rachou - FIOCRUZ-Minas, 1715 Augusto de Lima Av., Belo Horizonte, MG, Brazil.
authors.forename: Olindo Assis
authors.initials: OA
authors.lastname: Martins-Filho
authors.affiliation: Programa de Pós-Graduação em Imunologia Básica e Aplicada, Universidade Federal do Amazonas, 3000, Rodrigo Otávio Av., Manaus, AM, Brazil; Fundação de Hematologia e Hemoterapia do Amazonas - HEMOAM, 3497 Constantino Nery Av., Manaus, AM, Brazil. Electronic address: malheiroadriana@yahoo.com.br.
authors.forename: Adriana
authors.initials: A
authors.lastname: Malheiro
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics* / Q000254:growth & development; D019698:Hepatitis C, Chronic / Q000097:blood / Q000235:genetics* / Q000821:virology; D054884:Host-Pathogen Interactions; D006801:Humans; D007371:Interferon-gamma / Q000097:blood; D016753:Interleukin-10 / Q000097:blood / Q000235:genetics*; D020381:Interleukin-17 / Q000097:blood; D007376:Interleukin-2 / Q000097:blood; D015847:Interleukin-4 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood / Q000235:genetics*; D008297:Male; D011110:Polymorphism, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000235:genetics*
chemical_list: C508609:IL10 protein, human; C508717:IL17A protein, human; C508598:IL4 protein, human; C508600:IL6 protein, human; D020381:Interleukin-17; D007376:Interleukin-2; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma
keywords: HCV genotype; Interleukin-10; Interleukin-6; Polymorphism; Tumor necrosis factor-α