IFNL4 ss469415590 variant shows similar performance to rs12979860 as predictor of response to treatment against Hepatitis C Virus genotype 1 or 4 in Caucasians

PLoS One. 2014 Apr 18;9(4):e95515. doi: 10.1371/journal.pone.0095515. eCollection 2014.

Abstract

Objectives: The rs12979860 variant, linked to IL28B gene, predicts sustained viral response (SVR) to pegylated-interferon/ribavirin (pegIFN/RBV) therapy in Hepatitis C Virus genotype 1 or 4 (HCV-1/4)-infected patients. Recently, a functional variant, ss469415590, in linkage disequilibrium (LD) with rs12979860, has been discovered. Our objective was to assess the value of ss469415590 to predict SVR to pegIFN/RBV in Caucasian HCV-1/4-infected individuals and to compare its performance with that of rs12979860.

Methods: 272 Caucasian HCV-1/4-infected patients who completed a course of pegIFN/RBV were genotyped for both rs12979860 and ss469415590 markers. Logistic regression models including factors with univariate association with SVR and each genetic marker were elaborated. The area under the receiver operating-characteristic curve (AUROC) was calculated for each model and both were compared.

Results: Both markers were in LD (r2 = 0.82). For rs12979860, 66 (64.0%) CC versus 56 (33.1%) T allele carriers achieved SVR (Adjusted OR = 4.156, 95%CI = 2.388-7.232, p = 4.647×10-7). For ss469415590, 66 (66.0%) TT/TT versus 56 (32.5%) -G allele carriers (Adjusted OR = 4.783, 95%CI = 2.714-8.428, p = 6.153×10-8) achieved SVR. The AUROC of the model including rs12979860 was 0.742 (95%CI = 0.672-0.813) and of that based on ss469415590 was 0.756 (95%CI = 0.687-0.826) (p = 0.780).

Conclusions: The ss469415590 variant shows an equivalent performance to predict SVR to pegIFN/RBV than the rs2979860 in Caucasian HCV-1/4-infected patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alleles*
  • Antiviral Agents / therapeutic use*
  • Coinfection
  • Female
  • Follow-Up Studies
  • Genotype*
  • Hepacivirus / genetics*
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / genetics*
  • Hepatitis C, Chronic / virology
  • Humans
  • Interleukins / genetics*
  • Interleukins / therapeutic use*
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • ROC Curve
  • Treatment Outcome
  • White People / genetics

Substances

  • Antiviral Agents
  • IFNL4 protein, human
  • Interleukins

Grants and funding

This work was supported in part by the Red de Investigación en SIDA (ISCIII-RETIC RD12/0017), the Fundación Progreso y Salud, Consejería de Salud de la Junta de Andalucía (grant numbers PI-0247-2010, PI-0157/2011, PI-0430/2012), the Fondo de Investigaciones Sanitarias (grant numbers PI10/01664), the Ministerio de Sanidad y Servicios Sociales (EC11-304) and the Fundación para la Investigación y la Prevención del Sida en España (grant number 121004/10). Sara Borrell postdoctoral perfection grant from the Instituto de Salud Carlos III (grant number SCO/523/2008 to K.N.). Human resources grant from the Servicio de Salud de la Junta de Andalucía (grant number B-0037 to JMS). Intensification grant from the Instituto de Salud Carlos III (grant number Programa-I3SNS to J.A.P.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.