IL28 variation affects expression of interferon stimulated genes and peg-interferon and ribavirin therapy

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

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Abstract

Background & Aims: Common genetic variation within the IL28 locus has been found to influence the effect of peg-interferon and ribavirin combination therapy against chronic hepatitis C virus (HCV) infection. Expression of IL28 in peripheral blood cells has been reported to be higher in patients with IL28 SNP genotypes associated with favorable response. Methods: We analyzed 52 liver and 114 blood samples obtained from patients with HCV genotype 1b. We used reverse transcription-real time polymerase chain reaction to analyze expression levels of IL28 and several interferon stimulated genes (ISGs), including MxA, double stranded RNA dependent protein kinase (PKR), 2′-5′ oligo-nucleotide synthetase (OAS1), ISG15, and SOCS1. Results: Interestingly, expression of IL28 was significantly lower in patients with the response-favorable rs8099917 TT genotype compared to those with TG or GG genotypes (p <0.005). In hepatic cells, expression of MxA, PKR, OAS1, and ISG15 were also significantly lower in rs8099917 TT patients (p <0.001, p = 0.005, p = 0.001, p <0.001, respectively), whereas in peripheral blood mononuclear cells ISG expression levels did not differ significantly. Among patients treated with peg-interferon plus ribavirin therapy, liver mRNA levels of IL28, MxA, PKR, OAS1, and ISG15 were significantly or marginally lower in responders who became negative for HCV RNA (p = 0.001, 0.004, 0.014, 0.051, and 0.015, respectively). Conclusions: Expression levels of ISGs are differentially regulated in the liver and peripheral blood. The mechanism underlying the expression levels of IL28 and ISGs and the correlation with the effect of the therapy should be further investigated.

Original languageEnglish
Pages (from-to)1094-1101
Number of pages8
JournalJournal of Hepatology
Volume54
Issue number6
DOIs
Publication statusPublished - 01-06-2011

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Ribavirin
Interferons
Genotype
Hepacivirus
eIF-2 Kinase
Genes
Liver
Blood Cells
Therapeutics
Double-Stranded RNA
Chronic Hepatitis C
Virus Diseases
Ligases
Reverse Transcription
Single Nucleotide Polymorphism
Real-Time Polymerase Chain Reaction
Hepatocytes
Nucleotides
RNA
Gene Expression

All Science Journal Classification (ASJC) codes

  • Hepatology

Cite this

Abe, H., Hayes, C. N., Ochi, H., Maekawa, T., Tsuge, M., Miki, D., ... Chayama, K. (2011). IL28 variation affects expression of interferon stimulated genes and peg-interferon and ribavirin therapy. Journal of Hepatology, 54(6), 1094-1101. https://doi.org/10.1016/j.jhep.2010.09.019
Abe, Hiromi ; Hayes, C. Nelson ; Ochi, Hidenori ; Maekawa, Toshiro ; Tsuge, Masataka ; Miki, Daiki ; Mitsui, Fukiko ; Hiraga, Nobuhiko ; Imamura, Michio ; Takahashi, Shoichi ; Kubo, Michiaki ; Nakamura, Yusuke ; Chayama, Kazuaki. / IL28 variation affects expression of interferon stimulated genes and peg-interferon and ribavirin therapy. In: Journal of Hepatology. 2011 ; Vol. 54, No. 6. pp. 1094-1101.
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abstract = "Background & Aims: Common genetic variation within the IL28 locus has been found to influence the effect of peg-interferon and ribavirin combination therapy against chronic hepatitis C virus (HCV) infection. Expression of IL28 in peripheral blood cells has been reported to be higher in patients with IL28 SNP genotypes associated with favorable response. Methods: We analyzed 52 liver and 114 blood samples obtained from patients with HCV genotype 1b. We used reverse transcription-real time polymerase chain reaction to analyze expression levels of IL28 and several interferon stimulated genes (ISGs), including MxA, double stranded RNA dependent protein kinase (PKR), 2′-5′ oligo-nucleotide synthetase (OAS1), ISG15, and SOCS1. Results: Interestingly, expression of IL28 was significantly lower in patients with the response-favorable rs8099917 TT genotype compared to those with TG or GG genotypes (p <0.005). In hepatic cells, expression of MxA, PKR, OAS1, and ISG15 were also significantly lower in rs8099917 TT patients (p <0.001, p = 0.005, p = 0.001, p <0.001, respectively), whereas in peripheral blood mononuclear cells ISG expression levels did not differ significantly. Among patients treated with peg-interferon plus ribavirin therapy, liver mRNA levels of IL28, MxA, PKR, OAS1, and ISG15 were significantly or marginally lower in responders who became negative for HCV RNA (p = 0.001, 0.004, 0.014, 0.051, and 0.015, respectively). Conclusions: Expression levels of ISGs are differentially regulated in the liver and peripheral blood. The mechanism underlying the expression levels of IL28 and ISGs and the correlation with the effect of the therapy should be further investigated.",
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Abe, H, Hayes, CN, Ochi, H, Maekawa, T, Tsuge, M, Miki, D, Mitsui, F, Hiraga, N, Imamura, M, Takahashi, S, Kubo, M, Nakamura, Y & Chayama, K 2011, 'IL28 variation affects expression of interferon stimulated genes and peg-interferon and ribavirin therapy', Journal of Hepatology, vol. 54, no. 6, pp. 1094-1101. https://doi.org/10.1016/j.jhep.2010.09.019

IL28 variation affects expression of interferon stimulated genes and peg-interferon and ribavirin therapy. / Abe, Hiromi; Hayes, C. Nelson; Ochi, Hidenori; Maekawa, Toshiro; Tsuge, Masataka; Miki, Daiki; Mitsui, Fukiko; Hiraga, Nobuhiko; Imamura, Michio; Takahashi, Shoichi; Kubo, Michiaki; Nakamura, Yusuke; Chayama, Kazuaki.

In: Journal of Hepatology, Vol. 54, No. 6, 01.06.2011, p. 1094-1101.

Research output: Contribution to journalArticle

TY - JOUR

T1 - IL28 variation affects expression of interferon stimulated genes and peg-interferon and ribavirin therapy

AU - Abe, Hiromi

AU - Hayes, C. Nelson

AU - Ochi, Hidenori

AU - Maekawa, Toshiro

AU - Tsuge, Masataka

AU - Miki, Daiki

AU - Mitsui, Fukiko

AU - Hiraga, Nobuhiko

AU - Imamura, Michio

AU - Takahashi, Shoichi

AU - Kubo, Michiaki

AU - Nakamura, Yusuke

AU - Chayama, Kazuaki

PY - 2011/6/1

Y1 - 2011/6/1

N2 - Background & Aims: Common genetic variation within the IL28 locus has been found to influence the effect of peg-interferon and ribavirin combination therapy against chronic hepatitis C virus (HCV) infection. Expression of IL28 in peripheral blood cells has been reported to be higher in patients with IL28 SNP genotypes associated with favorable response. Methods: We analyzed 52 liver and 114 blood samples obtained from patients with HCV genotype 1b. We used reverse transcription-real time polymerase chain reaction to analyze expression levels of IL28 and several interferon stimulated genes (ISGs), including MxA, double stranded RNA dependent protein kinase (PKR), 2′-5′ oligo-nucleotide synthetase (OAS1), ISG15, and SOCS1. Results: Interestingly, expression of IL28 was significantly lower in patients with the response-favorable rs8099917 TT genotype compared to those with TG or GG genotypes (p <0.005). In hepatic cells, expression of MxA, PKR, OAS1, and ISG15 were also significantly lower in rs8099917 TT patients (p <0.001, p = 0.005, p = 0.001, p <0.001, respectively), whereas in peripheral blood mononuclear cells ISG expression levels did not differ significantly. Among patients treated with peg-interferon plus ribavirin therapy, liver mRNA levels of IL28, MxA, PKR, OAS1, and ISG15 were significantly or marginally lower in responders who became negative for HCV RNA (p = 0.001, 0.004, 0.014, 0.051, and 0.015, respectively). Conclusions: Expression levels of ISGs are differentially regulated in the liver and peripheral blood. The mechanism underlying the expression levels of IL28 and ISGs and the correlation with the effect of the therapy should be further investigated.

AB - Background & Aims: Common genetic variation within the IL28 locus has been found to influence the effect of peg-interferon and ribavirin combination therapy against chronic hepatitis C virus (HCV) infection. Expression of IL28 in peripheral blood cells has been reported to be higher in patients with IL28 SNP genotypes associated with favorable response. Methods: We analyzed 52 liver and 114 blood samples obtained from patients with HCV genotype 1b. We used reverse transcription-real time polymerase chain reaction to analyze expression levels of IL28 and several interferon stimulated genes (ISGs), including MxA, double stranded RNA dependent protein kinase (PKR), 2′-5′ oligo-nucleotide synthetase (OAS1), ISG15, and SOCS1. Results: Interestingly, expression of IL28 was significantly lower in patients with the response-favorable rs8099917 TT genotype compared to those with TG or GG genotypes (p <0.005). In hepatic cells, expression of MxA, PKR, OAS1, and ISG15 were also significantly lower in rs8099917 TT patients (p <0.001, p = 0.005, p = 0.001, p <0.001, respectively), whereas in peripheral blood mononuclear cells ISG expression levels did not differ significantly. Among patients treated with peg-interferon plus ribavirin therapy, liver mRNA levels of IL28, MxA, PKR, OAS1, and ISG15 were significantly or marginally lower in responders who became negative for HCV RNA (p = 0.001, 0.004, 0.014, 0.051, and 0.015, respectively). Conclusions: Expression levels of ISGs are differentially regulated in the liver and peripheral blood. The mechanism underlying the expression levels of IL28 and ISGs and the correlation with the effect of the therapy should be further investigated.

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