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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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.

元の言語English
ページ(範囲)1094-1101
ページ数8
ジャーナルJournal of Hepatology
54
発行部数6
DOI
出版物ステータスPublished - 06-2011

All Science Journal Classification (ASJC) codes

  • Hepatology

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    Abe, H., Hayes, C. N., 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, 54(6), 1094-1101. https://doi.org/10.1016/j.jhep.2010.09.019