title: Polymorphisms in histone deacetylases improve the predictive value of IL-28B for chronic hepatitis C therapy.
abstract: Histone deacetylases (HDACs) influence many cellular processes, including the modulation of signal transducer and activator of transcription activity (STAT) in response to interferon (IFN). To identify genetic markers that help optimize the IL-28B prediction of chronic hepatitis C (CHC) sustained virological response (SVR), we evaluated 27 single-nucleotide polymorphisms (SNPs) in HDAC1-11. Three SNPs, rs3778216, rs976552 and rs368328 in HDAC2, HDAC3 and HDAC5, respectively, were independently associated with SVR (P<0.05). The addition of these three HDAC's SNPs to the IL-28B predictive model (area under the curve (AUC)=0.630) rendered an important improvement of AUC-receiver operating characteristic value (AUC=0.747, P=0.021). Chi-squared Automatic Interaction Detector (CHAID) analysis denoted the significance of the rs3778216 C/C genotype in identifying a group of good responders despite carrying IL-28B T allele (79.2% of SVR), whereas HDAC5 G allele characterized a subgroup with poor response rate (25.5%). However, HDAC3 rs976552 did not display a relevant role for the hierarchical classification of patients. Variables related to SVR in hepatitis C virus genotype 1 (HCV-1) cohort were the same of those obtained for the overall population. Interestingly, in non-HCV-1 patients (n=56) the HDAC2 C/C genotype was the unique predictive variable related to SVR (AUC=0.733, P<0.007). Thus, these preliminary results suggest the potential usefulness of combined IL-28B and HDAC genotyping for the CHC patients' classification by likelihood of an SVR.
authors.affiliation: Liver Unit, Gastroenterology Service, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Universidad Autónoma de Madrid and CIBERehd, Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: R
authors.initials: R
authors.lastname: López-Rodríguez
authors.forename: Á
authors.initials: Á
authors.lastname: Hernández-Bartolomé
authors.forename: M J
authors.initials: MJ
authors.lastname: Borque
authors.forename: Y
authors.initials: Y
authors.lastname: Rodríguez-Muñoz
authors.forename: S
authors.initials: S
authors.lastname: Martín-Vílchez
authors.forename: M
authors.initials: M
authors.lastname: Trapero-Marugán
authors.forename: L
authors.initials: L
authors.lastname: García-Buey
authors.forename: P
authors.initials: P
authors.lastname: Muñoz de Rueda
authors.forename: L
authors.initials: L
authors.lastname: Rodrigo
authors.forename: J R
authors.initials: JR
authors.lastname: Vidal-Castiñeira
authors.forename: J
authors.initials: J
authors.lastname: Salmerón
authors.forename: R
authors.initials: R
authors.lastname: Moreno-Otero
authors.forename: P
authors.initials: P
authors.lastname: Sanz-Cameno
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000235:genetics / Q000821:virology; D006655:Histone Deacetylases / Q000235:genetics*; D006801:Humans; D016898:Interferon-alpha / Q000737:chemistry / Q000627:therapeutic use; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D007527:Isoenzymes / Q000235:genetics; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011092:Polyethylene Glycols / Q000737:chemistry; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D012254:Ribavirin / Q000627:therapeutic use; D016896:Treatment Outcome; D019562:Viral Load / Q000187:drug effects / Q000235:genetics; D055815:Young Adult; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D006655:Histone Deacetylases; D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D007527:Isoenzymes; D011092:Polyethylene Glycols; D012254:Ribavirin; C000624353:interferon-lambda, human; D000095022:Interferon Lambda