title: IL-18, TNF, and IFN-γ alleles and genotypes are associated with susceptibility to chronic hepatitis B infection and severity of liver injury.
abstract: This study evaluated the association of polymorphisms in the IL-18 (-607C/A and -137C/G), IFNγ (+874 A/T), and TNF (-238 A/G and -308 A/G) genes with susceptibility to HBV infection and severity of liver injury. A total of 259 chronic HBV-infected patients followed at the University Hospital, Faculty of Medicine of Ribeirão Preto, São Paulo, Brazil, and 202 healthy individuals were studied. Four Single Nucleotide Polymorphisms (SNPs) were amplified by Polymerase Chain Reaction (PCR). Liver biopsy was performed in 212 HBV-infected patients and classified according to severity of liver fibrosis (scores 0-4) and necroinflammatory activity (HAI scores 0-18). TNF-308*A allele (P < 0.001; OR = 2.16) and TNF -308 AA genotype (P = 0.026; OR = 5.43) were associated with susceptibility to HBV infection. An association was found between severe liver fibrosis when compared to mild fibrosis and the following polymorphisms: Alleles IL-18 -137*G (P = 0.004; OR = 3.45), TNF -308*A (P < 0.001; OR = 3.39), and IFNγ +874*T (P = 0.029; OR = 1.85) and IL-18 -137 GG genotype (P = 0.009; OR = 3.70). No significant association was found between IL-18 (-607 A/C) polymorphism and severity of liver fibrosis. Alleles IL-18 -137*G (P = 0.028; OR = 2.64) and TNF-308*A (P = 0.002; OR = 3.06) and IL-18 -137 GG genotype (P = 0.011; OR = 4.20) were associated with severe necroinflammatory activity (HAI>12) when compared to mild necroinflammatory activity (HAI 1-8). The results suggest that IL-18 -137C/G, TNF-308 G/A and IFNγ +874 A/T SNPs were associated to more severe liver injury in chronic HBV infection. TNF -308*A allele and TNF -308 AA genotype could play a role in the susceptibility to HBV infection.
authors.affiliation: Gastroenterology Division, Department of Medicine, Faculty of Medicine of Ribeirão Preto, University of São Paulo (FMRP-USP), Ribeirão Preto, São Paulo, Brazil.
authors.forename: Sandro da Costa
authors.initials: Sda C
authors.lastname: Ferreira
authors.affiliation: Gastroenterology Division, Department of Medicine, Faculty of Medicine of Ribeirão Preto, University of São Paulo (FMRP-USP), Ribeirão Preto, São Paulo, Brazil.|Department of Medicine, Federal University of São Carlos (UFSCAR), Ribeirão Preto, São Paulo, Brazil.
authors.forename: Silvana Gama Florêncio
authors.initials: SG
authors.lastname: Chachá
authors.affiliation: Gastroenterology Division, Department of Medicine, Faculty of Medicine of Ribeirão Preto, University of São Paulo (FMRP-USP), Ribeirão Preto, São Paulo, Brazil.
authors.forename: Fernanda Fernandes
authors.initials: FF
authors.lastname: Souza
authors.affiliation: Gastroenterology Division, Department of Medicine, Faculty of Medicine of Ribeirão Preto, University of São Paulo (FMRP-USP), Ribeirão Preto, São Paulo, Brazil.
authors.forename: Andreza Corrêa
authors.initials: AC
authors.lastname: Teixeira
authors.affiliation: Infectious Diseases Division, Department of Medicine, Faculty of Medicine of Ribeirão Preto, University of São Paulo (FMRP-USP), Ribeirão Preto, São Paulo, Brazil.
authors.forename: Rodrigo de Carvalho
authors.initials: Rde C
authors.lastname: Santana
authors.affiliation: Clinical Immunology Division, Department of Medicine, Faculty of Medicine of Ribeirão Preto, University of São Paulo (FMRP-USP), Ribeirão Preto, São Paulo, Brazil.
authors.forename: Neifi Hassan Saloun
authors.initials: NH
authors.lastname: Deghaide
authors.affiliation: Gastroenterology Division, Department of Medicine, Faculty of Medicine of Ribeirão Preto, University of São Paulo (FMRP-USP), Ribeirão Preto, São Paulo, Brazil.
authors.forename: Sandra
authors.initials: S
authors.lastname: Rodrigues
authors.affiliation: Genetics Department, Faculty of Medicine of Ribeirão Preto, University of São Paulo (FMRP-USP), Ribeirão Preto, São Paulo, Brazil.
authors.forename: Leonardo Arduíno
authors.initials: LA
authors.lastname: Marano
authors.affiliation: Departamento de Química - Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto (FFCLRP - USP), Ribeirão Preto, São Paulo, Brazil.
authors.forename: Celso Teixeira
authors.initials: CT
authors.lastname: Mendes-Junior
authors.affiliation: Pathology Department, Faculty of Medicine of Ribeirão Preto, University of São Paulo (FMRP-USP), Ribeirão Preto, São Paulo, Brazil.
authors.forename: Sérgio
authors.initials: S
authors.lastname: Zucoloto
authors.affiliation: Clinical Immunology Division, Department of Medicine, Faculty of Medicine of Ribeirão Preto, University of São Paulo (FMRP-USP), Ribeirão Preto, São Paulo, Brazil.
authors.forename: Eduardo Antônio
authors.initials: EA
authors.lastname: Donadi
authors.affiliation: Gastroenterology Division, Department of Medicine, Faculty of Medicine of Ribeirão Preto, University of São Paulo (FMRP-USP), Ribeirão Preto, São Paulo, Brazil.
authors.forename: Ana de Lourdes Candolo
authors.initials: Ade L
authors.lastname: Martinelli
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D001938:Brazil; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D019694:Hepatitis B, Chronic / Q000235:genetics* / Q000276:immunology / Q000473:pathology / Q000821:virology; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics* / Q000276:immunology; D020382:Interleukin-18 / Q000235:genetics* / Q000276:immunology; D008099:Liver / Q000276:immunology / Q000473:pathology / Q000503:physiopathology / Q000821:virology; D008103:Liver Cirrhosis / Q000235:genetics* / Q000821:virology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000276:immunology; D055815:Young Adult
chemical_list: D020382:Interleukin-18; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma
keywords: HBV infection; IFNγ; IL-18; TNF; cytokines; liver injury