title: Genetic variants of interferon-stimulated genes and IL-28B as host prognostic factors of response to combination treatment for chronic hepatitis C.
abstract: Chronic hepatitis C (CHC) is a worldwide health problem that is highly related to liver fibrosis, cirrhosis, and hepatocellular carcinoma. The achievement of response to the current standard of care-pegylated interferon plus ribavirin-has recently been described to be associated with single-nucleotide polymorphisms (SNPs) near the IL-28B gene. Additionally, baseline expression levels of genes involved in interferon (IFN)-stimulated genes (ISGs) have been found to be related to treatment outcome. In the present study, 285 patients were genotyped for 63 SNPs within genes of the IFN signaling pathway (IPGs) and ISGs. Two ISG polymorphisms-OASL rs12819210 (odds ratio (OR)=2.1, P=0.03) and IFIT1 rs304478 (OR=2.5, P=0.01)-were found to be independent predictive factors of sustained virological response (SVR) after adjusting for other clinical covariates. Furthermore, the predictive value of IL-28B SNP was notably improved by simultaneous genotyping of rs12819210 and rs304478, particularly in patients with the worst prognosis (viral genotype 1, area under the curve (AUC)=0.74). In conclusion, ISG SNPs could constitute a valuable tool for individualizing CHC therapy.
authors: Liver Unit, Gastroenterology Service, Hospital Universitario de La Princesa, Instituto de Investigación Sanitario Princesa, Universidad Autónoma de Madrid, Madrid, Spain.
authors: R
authors: R
authors: Lopez-Rodriguez
authors: M
authors: M
authors: Trapero-Marugan
authors: M J
authors: MJ
authors: Borque
authors: M
authors: M
authors: Roman
authors: A
authors: A
authors: Hernandez-Bartolome
authors: Y
authors: Y
authors: Rodriguez-Muñoz
authors: S
authors: S
authors: Martin-Vilchez
authors: F
authors: F
authors: Abad-Santos
authors: P
authors: P
authors: Muñoz de Rueda
authors: J R
authors: JR
authors: Vidal-Castiñeira
authors: L
authors: L
authors: Rodrigo
authors: J
authors: J
authors: Salmeron
authors: R
authors: R
authors: Moreno-Otero
authors: P
authors: P
authors: Sanz-Cameno
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D014644:Genetic Variation; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use; D007372:Interferons / Q000235:genetics*; D007378:Interleukins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D011994:Recombinant Proteins / Q000627:therapeutic use; D012189:Retrospective Studies; D012254:Ribavirin / Q000627:therapeutic use; D015398:Signal Transduction / Q000235:genetics*; D016896:Treatment Outcome; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D011092:Polyethylene Glycols; D011994:Recombinant Proteins; D012254:Ribavirin; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C417083:peginterferon alfa-2b; C100416:peginterferon alfa-2a