title: SOCS-1 promoter methylation and treatment response in chronic hepatitis C patients receiving pegylated-interferon/ribavirin.
abstract: OBJECTIVE
  Suppressor of cytokine signaling-1 (SOCS-1) is a negative regulator of the Janus kinase/signal transducer and activation of transcription pathway. The purpose of this study was to investigate the relationship between methylation of SOCS-1 and sustained virologic response (SVR) in chronic hepatitis C (CHC) patients treated with pegylated interferon (PEG-IFN)-alpha and ribavirin (RBV).
  
  
  METHODS
  In total, 106 CHC patients treated with PEG-IFN-alpha and RBV were included. Serum samples were obtained at baseline (P), end of treatment (EOT), and 6 months post treatment (F6). Methylation status of the promoter region of SOCS-1 was examined by quantitative methylation specific PCR (qMSP).
  
  
  RESULTS
  Median baseline methylation level of SOCS-1 was -0.95 log10 copies/mL, which increased to 0.57 log10 copies/mL at EOT and then returned to -0.57 log10 copies/mL at F6 (baseline vs EOT, P < 0.001; EOT vs F6, P < 0.001). The overall SVR was 75.5%. Univariate analysis indicated that SVR was significantly associated with genotype, baseline HCV RNA, body mass index (BMI) and higher EOT SOCS-1 methylation. Multivariate analysis confirmed that the SVR was significantly associated with genotype (OR: 13.40, 95% CI: 1.73-103.58, P = 0.013), baseline HCV RNA (OR: 0.19, 95% CI: 0.06-0.59, P = 0.004), BMI (OR: 0.73, 95% CI: 0.56-0.96, P = 0.022), and EOT SOCS-1 methylation (OR: 1.71, 95% CI: 1.11-2.62, P = 0.014).
  
  
  CONCLUSIONS
  CHC patients with significantly higher SOCS-1 methylation at the end of treatment had better SVRs. The role of SOCS-1 methylation in affecting treatment response deserves further investigation.
authors.affiliation: Department of Internal Medicine, Buddhist Dalin Tzu Chi General Hospital, Chia-Yi, Taiwan.
authors.forename: Kuo-Chih
authors.initials: KC
authors.lastname: Tseng
authors.forename: Jian-Liang
authors.initials: JL
authors.lastname: Chou
authors.forename: Hsien-Bin
authors.initials: HB
authors.lastname: Huang
authors.forename: Chih-Wei
authors.initials: CW
authors.lastname: Tseng
authors.forename: Shu-Fen
authors.initials: SF
authors.lastname: Wu
authors.forename: Michael W Y
authors.initials: MW
authors.lastname: Chan
mesh_terms: D000328:Adult; D019175:DNA Methylation / Q000187:drug effects; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D016174:Hepacivirus; D019698:Hepatitis C, Chronic / Q000628:therapy*; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011401:Promoter Regions, Genetic / Q000235:genetics; D012367:RNA, Viral / Q000235:genetics; D011994:Recombinant Proteins / Q000627:therapeutic use; D012254:Ribavirin / Q000627:therapeutic use*; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics*
chemical_list: D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; C108944:SOCS1 protein, human; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a