Global transcriptional response to interferon is a determinant of HCV treatment outcome and is modified by race

Xiao Song He, Xuhuai Ji, Matthew B. Hale, Ramsey Cheung, Aijaz Ahmed, Yaqian Guo, Garry P. Nolan, Lawrence Pfeffer, Teresa L. Wright, Neil Risch, Robert Tibshirani, Harry B. Greenberg

Research output: Contribution to journalArticle

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Abstract

Interferon (IFN)-α-based therapy for chronic hepatitis C is effective in fewer than 50% of all treated patients, with a substantially lower response rate in black patients. The goal of this study was to investigate the underlying host transcriptional response associated with interferon treatment outcomes. We collected peripheral blood mononuclear cells from chronic hepatitis C patients before initiation of IFN-α therapy and incubated the cells with or without IFN-α for 6 hours, followed by microarray assay to identify IFN-induced gene transcription. The microarray datasets were analyzed statistically according to the patients' race and virological responses to subsequent IFN-α treatment. The global induction of IFN-stimulated genes (ISGs) was significantly greater in sustained virological responders compared with nonresponders and in white patients compared with black patients. In addition, a significantly greater global induction of ISGs was observed in sustained virological responders compared with nonresponders within the group of white patients. The level of IFN-induced signal transducer and activator of transcription (STAT) 1 activation, a key component of the Janus kinase (JAK)-STAT signaling pathway, correlated with the global induction of ISGs and was significantly higher in white patients than in black patients. In conclusion, both treatment outcome and race are associated with different transcriptional responses to IFN-α. Because this difference is evident in the global induction of ISGs rather than a selective effect on a subset of such genes, key factors affecting the outcome of IFN-α therapy are likely to act at the JAK-STAT pathway that controls transcription of down-stream ISGs.

Original languageEnglish (US)
Pages (from-to)352-359
Number of pages8
JournalHepatology
Volume44
Issue number2
DOIs
StatePublished - Aug 1 2006

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Interferons
Genes
Janus Kinases
Chronic Hepatitis C
Transducers
STAT1 Transcription Factor
Cell- and Tissue-Based Therapy
Transcriptional Activation
Blood Cells
Therapeutics

All Science Journal Classification (ASJC) codes

  • Hepatology

Cite this

He, X. S., Ji, X., Hale, M. B., Cheung, R., Ahmed, A., Guo, Y., ... Greenberg, H. B. (2006). Global transcriptional response to interferon is a determinant of HCV treatment outcome and is modified by race. Hepatology, 44(2), 352-359. https://doi.org/10.1002/hep.21267

Global transcriptional response to interferon is a determinant of HCV treatment outcome and is modified by race. / He, Xiao Song; Ji, Xuhuai; Hale, Matthew B.; Cheung, Ramsey; Ahmed, Aijaz; Guo, Yaqian; Nolan, Garry P.; Pfeffer, Lawrence; Wright, Teresa L.; Risch, Neil; Tibshirani, Robert; Greenberg, Harry B.

In: Hepatology, Vol. 44, No. 2, 01.08.2006, p. 352-359.

Research output: Contribution to journalArticle

He, XS, Ji, X, Hale, MB, Cheung, R, Ahmed, A, Guo, Y, Nolan, GP, Pfeffer, L, Wright, TL, Risch, N, Tibshirani, R & Greenberg, HB 2006, 'Global transcriptional response to interferon is a determinant of HCV treatment outcome and is modified by race', Hepatology, vol. 44, no. 2, pp. 352-359. https://doi.org/10.1002/hep.21267
He, Xiao Song ; Ji, Xuhuai ; Hale, Matthew B. ; Cheung, Ramsey ; Ahmed, Aijaz ; Guo, Yaqian ; Nolan, Garry P. ; Pfeffer, Lawrence ; Wright, Teresa L. ; Risch, Neil ; Tibshirani, Robert ; Greenberg, Harry B. / Global transcriptional response to interferon is a determinant of HCV treatment outcome and is modified by race. In: Hepatology. 2006 ; Vol. 44, No. 2. pp. 352-359.
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