SOCS-1 promoter methylation and treatment response in chronic hepatitis C patients receiving pegylated-interferon/ribavirin

J Clin Immunol. 2013 Aug;33(6):1110-6. doi: 10.1007/s10875-013-9903-4. Epub 2013 May 24.

Abstract

Purpose: 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).

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • DNA Methylation / drug effects
  • Drug Resistance, Viral / genetics*
  • Female
  • Follow-Up Studies
  • Hepacivirus*
  • Hepatitis C, Chronic / therapy*
  • Humans
  • Immunotherapy / methods
  • Interferon-alpha / therapeutic use*
  • Male
  • Middle Aged
  • Polyethylene Glycols / therapeutic use*
  • Promoter Regions, Genetic / genetics
  • RNA, Viral / genetics
  • Recombinant Proteins / therapeutic use
  • Ribavirin / therapeutic use*
  • Suppressor of Cytokine Signaling 1 Protein
  • Suppressor of Cytokine Signaling Proteins / genetics*

Substances

  • Interferon-alpha
  • RNA, Viral
  • Recombinant Proteins
  • SOCS1 protein, human
  • Suppressor of Cytokine Signaling 1 Protein
  • Suppressor of Cytokine Signaling Proteins
  • Polyethylene Glycols
  • Ribavirin
  • peginterferon alfa-2a