Diversity of killer cell immunoglobulin-like receptor (KIR) genotypes and KIR2DL2/3 variants in HCV treatment outcome

PLoS One. 2014 Jun 13;9(6):e99426. doi: 10.1371/journal.pone.0099426. eCollection 2014.

Abstract

The aim of this study was to analyse the distribution of KIR haplotypes and the KIR2DL2/3 alleles in chronic HCV-infected patients in order to establish the influence on the response to pegylated interferon plus ribavirin classical treatment. The alleles study of previously associated KIR2DL2/3 showed that KIR2DL2*001 was more frequent in non-SVR (NSVR) (42.2% vs. 27.5%, p<0.05) and KIR2DL3*001 was associated with sustained viral response (SVR) (41.6% vs. 61.2%, p<0.005). The KIR2DL3*001-HLA-C1 association was also significant (24.5% vs. 45.7%, p<0.001). From the frequencies of KIR obtained, 35 genotypes were assigned on the basis of previous studies. The centromeric A/A genotype was more frequent in SVR (44.1% vs. 34.5%, p<0.005) and the centromeric B/B genotype was found to be significantly more frequent in NSVR (20.9% vs. 11.2%, p<0.001). The logic regression model showed the importance of KIR genes in predicting the response to combined treatment, since the positive predictive value (PPV) was improved (from 55.9% to 75.3%) when the analysis of KIR was included in addition to the IFNL3 rs12979860 polymorphism. The study of KIR receptors may be a powerful tool for predicting the combined treatment response in patients with chronic HCV infection in association with the determination of IFNL3 polymorphism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / therapeutic use*
  • Drug Therapy, Combination
  • Genotype
  • Haplotypes
  • Hepacivirus / drug effects
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / genetics
  • Hepatitis C, Chronic / virology
  • Humans
  • Interferon-alpha / therapeutic use*
  • Interferons
  • Interleukins / genetics
  • Killer Cells, Natural / immunology
  • Logistic Models
  • Polymorphism, Single Nucleotide
  • Receptors, KIR2DL2 / genetics*
  • Receptors, KIR2DL3 / genetics*
  • Ribavirin / therapeutic use*
  • Treatment Outcome

Substances

  • Antiviral Agents
  • interferon-lambda, human
  • Interferon-alpha
  • Interleukins
  • KIR2DL2 protein, human
  • KIR2DL3 protein, human
  • Receptors, KIR2DL2
  • Receptors, KIR2DL3
  • Ribavirin
  • Interferons

Grants and funding

Supported by Spanish grant PI12-02587 from the Instituto de Salud Carlos III, RETICS REDiNREN (RD12/0021/0021) from the Instituto de Salud Carlos III and by European Union “Fondos FEDER ”. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.