title: Vitamin D pathway gene variants and HCV-2/3 therapy outcomes.
abstract: BACKGROUND
  The combination of ribavirin and pegylated interferon-α is considered the standard of care for HCV-2/3 genotypes. The immune system plays a key role in the achievement of a sustained virological response (SVR). Vitamin D seems to influence antiviral response in chronic hepatitis C and its pathway is controlled by polymorphic genes such as CYP27B1, CYP24A1 and VDR. In this study, we have investigated the correlation among the treatment outcomes and single nucleotide polymorphisms (SNPs) in the above-mentioned genes and IL28B genes.
  
  
  METHODS
  A total of 112 HCV-2/3 patients treated with interferon plus ribavirin were retrospectively studied; allelic discrimination was performed by real-time PCR.
  
  
  RESULTS
  CYP24A1rs2585428, IL28Brs12979860 and rs8099917 SNPs affected treatment failure and body mass index (BMI), Metavir score, IL28Brs8099917TT and CYP24A1rs2585428GG were the only factors able to predict it. SVR was predicted by Metavir score, HCV RNA at baseline and early virological response (EVR). IL28Brs12979860 SNP and HCV RNA were also related to rapid virological response. EVR was predicted by BMI, Metavir score and CYP24A1rs2585428 SNP. IL28Brs8099917TT and FokITT were relapse prediction factors.
  
  
  CONCLUSIONS
  In addition to non-genetic factors, SNPs in the vitamin D pathway seem to have a role in HCV-2/3 therapy outcomes. This study reveals the likely usefulness of pharmacogenetic-based ribavirin and interferon therapy to help identify patients for whom therapy could be successful or not, also considering new future expensive therapy options. To date, no similar data were published on these viral genotypes, but further studies in different and bigger cohorts are needed.
authors.affiliation: Unit of Infectious Diseases, University of Turin, Department of Medical Sciences, Amedeo di Savoia Hospital, Turin, Italy. jessica.cusato@yahoo.it.
authors.forename: Jessica
authors.initials: J
authors.lastname: Cusato
authors.forename: Sarah
authors.initials: S
authors.lastname: Allegra
authors.forename: Lucio
authors.initials: L
authors.lastname: Boglione
authors.forename: Amedeo
authors.initials: A
authors.lastname: De Nicolò
authors.forename: Lorena
authors.initials: L
authors.lastname: Baietto
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Cariti
authors.forename: Giovanni
authors.initials: G
authors.lastname: Di Perri
authors.forename: Antonio
authors.initials: A
authors.lastname: D'Avolio
mesh_terms: D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000235:genetics; D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use; D005260:Female; D056726:Genetic Association Studies; D014644:Genetic Variation; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics*; D006526:Hepatitis C / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism* / Q000821:virology; D006801:Humans; D007372:Interferons; D007378:Interleukins / Q000235:genetics; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide; D018167:Receptors, Calcitriol / Q000235:genetics; D012189:Retrospective Studies; D015398:Signal Transduction; D016896:Treatment Outcome; D019562:Viral Load; D014807:Vitamin D / Q000378:metabolism*; D065668:Vitamin D3 24-Hydroxylase / Q000235:genetics; D000095022:Interferon Lambda
chemical_list: D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase; D000998:Antiviral Agents; D007372:Interferons; D007378:Interleukins; D018167:Receptors, Calcitriol; D014807:Vitamin D; D065668:Vitamin D3 24-Hydroxylase; C000624353:interferon-lambda, human; D000095022:Interferon Lambda