Inverse association of IL28B genotype and liver mRNA expression of genes promoting or suppressing antiviral state

Hiromi Abe, C. Nelson Hayes, Hidenori Ochi, Masataka Tsuge, Daiki Miki, Nobuhiko Hiraga, Michio Imamura, Shoichi Takahashi, Michiaki Kubo, Yusuke Nakamura, Naoyuki Kamatani, Kazuaki Chayama

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

High intrahepatic expression levels of interferon stimulated genes (ISGs) in chronic hepatitis C patients are associated with poor response to interferon plus ribavirin combination therapy. Expression levels of 16 genes (OAS1, PKR, MxA, ISG15, RIG-I, TLR8, IRF7, IRF9, NFKBIA, IL28A/IL28B, IL29, IL28RA, IL10RB, IFNAR2, and STAT1) that promote antiviral state and 4 genes (SOCS1, SOCS3, Zc3h12a, and A20) that suppress antiviral state were analyzed using real-time PCR assays in 133 liver biopsy samples from patients infected with genotypes 1 or 2. Expression levels of genes promoting antiviral state were positively correlated with each other but were not correlated with those that suppress antiviral state. Expression levels of some ISGs were inversely associated with common polymorphisms within the IL28B locus. Genes promoting antiviral state were expressed lower (e.g., ISG15, P=1.42E-12 and MxA, P=6.40E-11) in individuals with the protective rs12979860 CC genotype, and genes suppressing antiviral state were expressed higher (A20, P=0.00107 and Zc3h12a, P=0.00129, respectively), although some ISGs were not significant after the Bonferroni correction. The expression levels of both an antiviral (MxA) and a suppressor (SOCS1) ISG were independent predictors for non-response. These results suggest that rs12979860 genotype may be associated with response to combination therapy through an inverse relationship between antiviral and suppressor ISGs in the liver.

Original languageEnglish
Pages (from-to)1597-1607
Number of pages11
JournalJournal of Medical Virology
Volume83
Issue number9
DOIs
Publication statusPublished - 01-09-2011

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Antiviral Agents
Genotype
Gene Expression
Messenger RNA
Interferons
Liver
Genes
Ribavirin
Chronic Hepatitis C
Real-Time Polymerase Chain Reaction
Biopsy
Therapeutics

All Science Journal Classification (ASJC) codes

  • Virology
  • Infectious Diseases

Cite this

Abe, Hiromi ; Hayes, C. Nelson ; Ochi, Hidenori ; Tsuge, Masataka ; Miki, Daiki ; Hiraga, Nobuhiko ; Imamura, Michio ; Takahashi, Shoichi ; Kubo, Michiaki ; Nakamura, Yusuke ; Kamatani, Naoyuki ; Chayama, Kazuaki. / Inverse association of IL28B genotype and liver mRNA expression of genes promoting or suppressing antiviral state. In: Journal of Medical Virology. 2011 ; Vol. 83, No. 9. pp. 1597-1607.
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abstract = "High intrahepatic expression levels of interferon stimulated genes (ISGs) in chronic hepatitis C patients are associated with poor response to interferon plus ribavirin combination therapy. Expression levels of 16 genes (OAS1, PKR, MxA, ISG15, RIG-I, TLR8, IRF7, IRF9, NFKBIA, IL28A/IL28B, IL29, IL28RA, IL10RB, IFNAR2, and STAT1) that promote antiviral state and 4 genes (SOCS1, SOCS3, Zc3h12a, and A20) that suppress antiviral state were analyzed using real-time PCR assays in 133 liver biopsy samples from patients infected with genotypes 1 or 2. Expression levels of genes promoting antiviral state were positively correlated with each other but were not correlated with those that suppress antiviral state. Expression levels of some ISGs were inversely associated with common polymorphisms within the IL28B locus. Genes promoting antiviral state were expressed lower (e.g., ISG15, P=1.42E-12 and MxA, P=6.40E-11) in individuals with the protective rs12979860 CC genotype, and genes suppressing antiviral state were expressed higher (A20, P=0.00107 and Zc3h12a, P=0.00129, respectively), although some ISGs were not significant after the Bonferroni correction. The expression levels of both an antiviral (MxA) and a suppressor (SOCS1) ISG were independent predictors for non-response. These results suggest that rs12979860 genotype may be associated with response to combination therapy through an inverse relationship between antiviral and suppressor ISGs in the liver.",
author = "Hiromi Abe and Hayes, {C. Nelson} and Hidenori Ochi and Masataka Tsuge and Daiki Miki and Nobuhiko Hiraga and Michio Imamura and Shoichi Takahashi and Michiaki Kubo and Yusuke Nakamura and Naoyuki Kamatani and Kazuaki Chayama",
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Abe, H, Hayes, CN, Ochi, H, Tsuge, M, Miki, D, Hiraga, N, Imamura, M, Takahashi, S, Kubo, M, Nakamura, Y, Kamatani, N & Chayama, K 2011, 'Inverse association of IL28B genotype and liver mRNA expression of genes promoting or suppressing antiviral state', Journal of Medical Virology, vol. 83, no. 9, pp. 1597-1607. https://doi.org/10.1002/jmv.22158

Inverse association of IL28B genotype and liver mRNA expression of genes promoting or suppressing antiviral state. / Abe, Hiromi; Hayes, C. Nelson; Ochi, Hidenori; Tsuge, Masataka; Miki, Daiki; Hiraga, Nobuhiko; Imamura, Michio; Takahashi, Shoichi; Kubo, Michiaki; Nakamura, Yusuke; Kamatani, Naoyuki; Chayama, Kazuaki.

In: Journal of Medical Virology, Vol. 83, No. 9, 01.09.2011, p. 1597-1607.

Research output: Contribution to journalArticle

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T1 - Inverse association of IL28B genotype and liver mRNA expression of genes promoting or suppressing antiviral state

AU - Abe, Hiromi

AU - Hayes, C. Nelson

AU - Ochi, Hidenori

AU - Tsuge, Masataka

AU - Miki, Daiki

AU - Hiraga, Nobuhiko

AU - Imamura, Michio

AU - Takahashi, Shoichi

AU - Kubo, Michiaki

AU - Nakamura, Yusuke

AU - Kamatani, Naoyuki

AU - Chayama, Kazuaki

PY - 2011/9/1

Y1 - 2011/9/1

N2 - High intrahepatic expression levels of interferon stimulated genes (ISGs) in chronic hepatitis C patients are associated with poor response to interferon plus ribavirin combination therapy. Expression levels of 16 genes (OAS1, PKR, MxA, ISG15, RIG-I, TLR8, IRF7, IRF9, NFKBIA, IL28A/IL28B, IL29, IL28RA, IL10RB, IFNAR2, and STAT1) that promote antiviral state and 4 genes (SOCS1, SOCS3, Zc3h12a, and A20) that suppress antiviral state were analyzed using real-time PCR assays in 133 liver biopsy samples from patients infected with genotypes 1 or 2. Expression levels of genes promoting antiviral state were positively correlated with each other but were not correlated with those that suppress antiviral state. Expression levels of some ISGs were inversely associated with common polymorphisms within the IL28B locus. Genes promoting antiviral state were expressed lower (e.g., ISG15, P=1.42E-12 and MxA, P=6.40E-11) in individuals with the protective rs12979860 CC genotype, and genes suppressing antiviral state were expressed higher (A20, P=0.00107 and Zc3h12a, P=0.00129, respectively), although some ISGs were not significant after the Bonferroni correction. The expression levels of both an antiviral (MxA) and a suppressor (SOCS1) ISG were independent predictors for non-response. These results suggest that rs12979860 genotype may be associated with response to combination therapy through an inverse relationship between antiviral and suppressor ISGs in the liver.

AB - High intrahepatic expression levels of interferon stimulated genes (ISGs) in chronic hepatitis C patients are associated with poor response to interferon plus ribavirin combination therapy. Expression levels of 16 genes (OAS1, PKR, MxA, ISG15, RIG-I, TLR8, IRF7, IRF9, NFKBIA, IL28A/IL28B, IL29, IL28RA, IL10RB, IFNAR2, and STAT1) that promote antiviral state and 4 genes (SOCS1, SOCS3, Zc3h12a, and A20) that suppress antiviral state were analyzed using real-time PCR assays in 133 liver biopsy samples from patients infected with genotypes 1 or 2. Expression levels of genes promoting antiviral state were positively correlated with each other but were not correlated with those that suppress antiviral state. Expression levels of some ISGs were inversely associated with common polymorphisms within the IL28B locus. Genes promoting antiviral state were expressed lower (e.g., ISG15, P=1.42E-12 and MxA, P=6.40E-11) in individuals with the protective rs12979860 CC genotype, and genes suppressing antiviral state were expressed higher (A20, P=0.00107 and Zc3h12a, P=0.00129, respectively), although some ISGs were not significant after the Bonferroni correction. The expression levels of both an antiviral (MxA) and a suppressor (SOCS1) ISG were independent predictors for non-response. These results suggest that rs12979860 genotype may be associated with response to combination therapy through an inverse relationship between antiviral and suppressor ISGs in the liver.

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