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SOCS-1 Promoter Methylation and Treatment Response in Chronic Hepatitis C Patients Receiving Pegylated-Interferon/Ribavirin

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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.

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Abbreviations

HCV:

Hepatitis C virus

CHC:

Chronic hepatitis C

HCC:

Hepatocellular carcinoma

PEG-IFN:

Pegylated interferon

RBV:

Ribavirin

SVR:

Sustained virologic response

BMI:

Body mass index

ALT:

Alanine aminotransferase

SNPs:

Single nucleotide polymorphisms

IL-28B:

Interleukin-28B

SOCS:

Suppressors of cytokine signaling

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Acknowledgments

This study was supported by research grant from Dalin Tzu Chi Buddist Hospital (DTCRD97(2)-10), College of Science, National Chung Cheng University and National Science Council (NSC100-2320-B-194-002), Taiwan.

Disclosure

The authors declare no conflicts of interest.

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Corresponding author

Correspondence to Michael W. Y. Chan.

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Figure S1

Immunohistochemistry examination of SOCS-1 in liver biopsy from chronic hepatitis C patients. Sample with lower serum level of methylated SOCS-1 DNA (A1, 100×) have higher expression of SOCS-1 as shown by strong cytoplasmic staining; while sample with higher serum level of methylated SOCS-1 DNA (B1, 100×) have lower expression of SOCS-1. The high power images in the selected area are also shown (A2, B2, 400×). (PPT 627 kb)

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Tseng, KC., Chou, JL., Huang, HB. et al. SOCS-1 Promoter Methylation and Treatment Response in Chronic Hepatitis C Patients Receiving Pegylated-Interferon/Ribavirin. J Clin Immunol 33, 1110–1116 (2013). https://doi.org/10.1007/s10875-013-9903-4

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  • DOI: https://doi.org/10.1007/s10875-013-9903-4

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