title: IFNL4 ss469415590 variant shows similar performance to rs12979860 as predictor of response to treatment against Hepatitis C Virus genotype 1 or 4 in Caucasians.
abstract: OBJECTIVE
  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.
authors.affiliation: Unidad Clínica de Enfermedades Infecciosas y Microbiología. Hospital Universitario de Valme, Sevilla, Spain; Instituto de Biomedicina de Sevilla (IBIS), Sevilla, Spain.
authors.forename: Luis M
authors.initials: LM
authors.lastname: Real
authors.affiliation: Unidad Clínica de Enfermedades Infecciosas y Microbiología. Hospital Universitario de Valme, Sevilla, Spain; Instituto de Biomedicina de Sevilla (IBIS), Sevilla, Spain.
authors.forename: Karin
authors.initials: K
authors.lastname: Neukam
authors.affiliation: Unidad de Inmunogenética, Universidad de Jaén, Jaén, Spain.
authors.forename: Rocío
authors.initials: R
authors.lastname: Herrero
authors.affiliation: Servicio de Medicina Interna. Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
authors.forename: Josep M
authors.initials: JM
authors.lastname: Guardiola
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Vienna HIV & Liver Study Group, Vienna, Austria.
authors.forename: Thomas
authors.initials: T
authors.lastname: Reiberger
authors.affiliation: Unidad de Enfermedades Infecciosas, Hospital Universitario Reina Sofía, Córdoba, Spain; Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBC), Córdoba, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Rivero-Juarez
authors.affiliation: Servicio de Medicina Interna. Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
authors.forename: Juliana
authors.initials: J
authors.lastname: Salazar
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Vienna HIV & Liver Study Group, Vienna, Austria.
authors.forename: Mattias
authors.initials: M
authors.lastname: Mandorfer
authors.affiliation: Unidad de Enfermedades Infecciosas. Hospital Juan Ramón Jiménez, Huelva, Spain.
authors.forename: Dolores
authors.initials: D
authors.lastname: Merino
authors.affiliation: Departamento de Enfermedades Infecciosas. Hospital Carlos III, Madrid, Spain.
authors.forename: Vicente
authors.initials: V
authors.lastname: Soriano
authors.affiliation: Unidad de Enfermedades Infecciosas, Hospital Universitario Reina Sofía, Córdoba, Spain; Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBC), Córdoba, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Rivero
authors.affiliation: Unidad Clínica de Enfermedades Infecciosas y Microbiología. Hospital Universitario de Valme, Sevilla, Spain; Instituto de Biomedicina de Sevilla (IBIS), Sevilla, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Macías
authors.affiliation: Unidad Clínica de Enfermedades Infecciosas y Microbiología. Hospital Universitario de Valme, Sevilla, Spain; Instituto de Biomedicina de Sevilla (IBIS), Sevilla, Spain.
authors.forename: Juan A
authors.initials: JA
authors.lastname: Pineda
authors.affiliation: Unidad de Inmunogenética, Universidad de Jaén, Jaén, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Caruz
mesh_terms: D000328:Adult; D000483:Alleles; D000998:Antiviral Agents / Q000627:therapeutic use*; D060085:Coinfection; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000235:genetics* / Q000821:virology; D006801:Humans; D007378:Interleukins / Q000235:genetics* / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012372:ROC Curve; D016896:Treatment Outcome; D044465:White People / Q000235:genetics; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D007378:Interleukins; C579163:IFNL4 protein, human; D000095022:Interferon Lambda
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