HCV-related liver and lymphoproliferative diseases: association with polymorphisms of IL28B and TLR2

Oncotarget. 2016 Jun 21;7(25):37487-37497. doi: 10.18632/oncotarget.9303.

Abstract

To explore the relationship between innate immunity and hepatitis C Virus (HCV) in determining the risk of cirrhosis (CIR), hepatocellular carcinoma (HCC), mixed cryoglobulinemia syndrome (MCS) and non-Hodgkin lymphoma (NHL), we investigated the impact of the toll-like receptor-2 (TLR2) and interleukin-28B (IL28B) genetic variants. TLR2 -174 del variant was associated with TLR2 expression and with specific downstream molecules that drive the expression of different interleukins; rs12979860 Il28B was important in response to interferon-treatment and in spontaneous clearance of HCV. The risk for liver and lymphoproliferative diseases in HCV progression was clarified by stratifying 862 HCV-positive patients into groups based on liver (CIR, HCC) and lymphoproliferative HCV-related diseases (MCS, NHL) and compared with chronic HCV (CHC) infection. Analysis of TLR2-IL28B haplotypes showed an association of wild type haplotype with the lymphoproliferative diseases (OR 1.77, p = 0.029) and a slight increase in HCV viral load (HR 1.38, p = 0.054). Wild type haplotype (TLR2 ins/ins- IL28B C/C) was also found associated with older age in patients with an hepatic diseases (in CIR and in HCC p = 0.038 and p = 0.020, respectively) supporting an effect of innate immunity in the liver disease progression. TLR2 and IL28B polymorphisms in combination showed a role in the control of HCV viral load and different HCV disease progression.

Keywords: HCC; HCV; IL28B; Immune response; Immunity; Immunology and Microbiology Section; NHL; TLR2.

MeSH terms

  • Adult
  • Aged
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / pathology
  • Carcinoma, Hepatocellular / virology
  • Case-Control Studies
  • Female
  • Genotype
  • Hepacivirus / genetics
  • Hepacivirus / isolation & purification*
  • Hepatitis C, Chronic / genetics*
  • Hepatitis C, Chronic / pathology
  • Hepatitis C, Chronic / virology
  • Humans
  • Interferons
  • Interleukins / genetics*
  • Liver Neoplasms / genetics
  • Liver Neoplasms / pathology
  • Liver Neoplasms / virology
  • Lymphoproliferative Disorders / genetics*
  • Lymphoproliferative Disorders / pathology
  • Lymphoproliferative Disorders / virology*
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Toll-Like Receptor 2 / genetics*

Substances

  • IFNL3 protein, human
  • Interleukins
  • TLR2 protein, human
  • Toll-Like Receptor 2
  • Interferons