IFNL3 (IL28B) and IFNL4 polymorphisms are associated with treatment response in Thai patients infected with HCV genotype 1, but not with genotypes 3 and 6

J Med Virol. 2014 Sep;86(9):1482-90. doi: 10.1002/jmv.23957. Epub 2014 Apr 30.

Abstract

Recent studies have shown an association between single nucleotide polymorphisms (SNPs) in the interferon lambda-3 (IFNL3 or IL-28B) and IFNL4 genes and treatment response to hepatitis C virus genotype 1 (HCV-1) infection. The importance of these SNPs for HCV genotype 3 (HCV-3), and particularly HCV genotype 6 (HCV-6), remains to be elucidated. We analyzed a cohort of 225 Thai individuals with chronic HCV infection treated with pegylated-interferon and ribavirin, of whom 69 (30.7%), 114 (50.7%) and 42 (18.6%) patients were infected with HCV-1, HCV-3, and HCV-6, respectively. DNA extracted from blood samples was analyzed for the SNPs rs12979860 and ss469415590. The distribution of CC, CT, and TT genotypes of rs12979860 was 189 (84%), 28 (12.4%) and 8 (3.6%), respectively, while the distribution of TT/TT, ΔG/TT, and ΔG/ΔG genotypes of ss469415590 was 192(85.3%), 28(12.5%), and 5(2.2%), respectively. Significantly lower frequencies of the favorable genotypes CC (for rs12979860) and TT/TT (for ss469415590) were found in the HCV-1 group in comparison with the other groups. The favorable genotypes were associated significantly with rapid and sustained virological response in the HCV-1 group. However, they were only associated with rapid virological response in the HCV-3 and HCV-6 groups. Furthermore, both SNPs were associated equally with the treatment outcome in the HCV-1 group. In contrast, the role of these SNPs in predicting treatment response was attenuated in the HCV-3 and HCV-6 groups. Thus, identification of these SNPs may be useful only in patients with refractory HCV-1 infection.

Keywords: interferon lambda-3; interferon lambda-4; interleukin 28B; single nucleotide polymorphisms; sustained virological response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antiviral Agents / therapeutic use
  • Female
  • Genetic Association Studies
  • Genotype
  • Hepacivirus / genetics*
  • Hepatitis C, Chronic / drug therapy
  • Hepatitis C, Chronic / genetics*
  • Humans
  • Interferon alpha-2
  • Interferon-alpha / therapeutic use
  • Interferons
  • Interleukins / genetics*
  • Male
  • Middle Aged
  • Polyethylene Glycols / therapeutic use
  • Polymorphism, Single Nucleotide*
  • Recombinant Proteins / therapeutic use
  • Ribavirin / therapeutic use
  • Thailand
  • Treatment Outcome

Substances

  • Antiviral Agents
  • interferon-lambda, human
  • IFNL4 protein, human
  • Interferon alpha-2
  • Interferon-alpha
  • Interleukins
  • Recombinant Proteins
  • Polyethylene Glycols
  • Ribavirin
  • Interferons
  • peginterferon alfa-2b
  • peginterferon alfa-2a