BACKGROUND/AIMS: Interferon signaling pathway genes (IPGs) and interferon-stimulated genes (ISGs) are associated with the host response to hepatitis C virus (HCV) infection. We studied single nucleotide polymorphisms (SNPs) in IPGs and ISGs for their associations with response to pegylated interferon alpha-2a (Peg-IFN-alpha) plus ribavirin therapy in HCV genotype-1 infected patients. METHODS: A two-stage study design was used. First, out of 118 SNPs selected, 91 SNPs from 5 IPGs and 12 ISGs were genotyped in a cohort of 374 treatment-naïve HCV patients and assessed for association with sustained virologic response (SVR). Next, 14 potentially functional SNPs from the OASL gene were studied in this cohort. RESULTS: Three OASL SNPs (rs3213545 and rs1169279 from stage I, and rs2859398 from stage II), were significantly associated with SVR [rs3213545: p=0.03, RR=1.27 (1.03-1.58); rs1169279: p=0.02, RR=1.32 (1.05-1.65) p=0.02; rs2859398: p=0.02, RR=1.29 (1.04-1.61)] after adjusting for other covariates. Further analysis showed that these three SNPs independently associated with SVR. Additionally, a similar trend towards the associations of these three SNPs with SVR was observed in a smaller, independent HCV cohort consisting of subjects from a number of clinical practice settings. CONCLUSIONS: Our study suggests that OASL variants are involved in the host response to IFN-based therapy in HCV patients.
BACKGROUND/AIMS: Interferon signaling pathway genes (IPGs) and interferon-stimulated genes (ISGs) are associated with the host response to hepatitis C virus (HCV) infection. We studied single nucleotide polymorphisms (SNPs) in IPGs and ISGs for their associations with response to pegylated interferon alpha-2a (Peg-IFN-alpha) plus ribavirin therapy in HCV genotype-1 infectedpatients. METHODS: A two-stage study design was used. First, out of 118 SNPs selected, 91 SNPs from 5 IPGs and 12 ISGs were genotyped in a cohort of 374 treatment-naïve HCVpatients and assessed for association with sustained virologic response (SVR). Next, 14 potentially functional SNPs from the OASL gene were studied in this cohort. RESULTS: Three OASL SNPs (rs3213545 and rs1169279 from stage I, and rs2859398 from stage II), were significantly associated with SVR [rs3213545: p=0.03, RR=1.27 (1.03-1.58); rs1169279: p=0.02, RR=1.32 (1.05-1.65) p=0.02; rs2859398: p=0.02, RR=1.29 (1.04-1.61)] after adjusting for other covariates. Further analysis showed that these three SNPs independently associated with SVR. Additionally, a similar trend towards the associations of these three SNPs with SVR was observed in a smaller, independent HCV cohort consisting of subjects from a number of clinical practice settings. CONCLUSIONS: Our study suggests that OASL variants are involved in the host response to IFN-based therapy in HCVpatients.
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Authors: A Danielle Iuliano; Eleanor Feingold; Abdus S Wahed; David E Kleiner; Steven H Belle; Hari S Conjeevaram; Joseph Zmuda; T Jake Liang; Leland J Yee Journal: Intervirology Date: 2009-04-25 Impact factor: 1.763
Authors: Hideaki Tahara; Marimo Sato; Magdalena Thurin; Ena Wang; Lisa H Butterfield; Mary L Disis; Bernard A Fox; Peter P Lee; Samir N Khleif; Jon M Wigginton; Stefan Ambs; Yasunori Akutsu; Damien Chaussabel; Yuichiro Doki; Oleg Eremin; Wolf Hervé Fridman; Yoshihiko Hirohashi; Kohzoh Imai; James Jacobson; Masahisa Jinushi; Akira Kanamoto; Mohammed Kashani-Sabet; Kazunori Kato; Yutaka Kawakami; John M Kirkwood; Thomas O Kleen; Paul V Lehmann; Lance Liotta; Michael T Lotze; Michele Maio; Anatoli Malyguine; Giuseppe Masucci; Hisahiro Matsubara; Shawmarie Mayrand-Chung; Kiminori Nakamura; Hiroyoshi Nishikawa; A Karolina Palucka; Emanuel F Petricoin; Zoltan Pos; Antoni Ribas; Licia Rivoltini; Noriyuki Sato; Hiroshi Shiku; Craig L Slingluff; Howard Streicher; David F Stroncek; Hiroya Takeuchi; Minoru Toyota; Hisashi Wada; Xifeng Wu; Julia Wulfkuhle; Tomonori Yaguchi; Benjamin Zeskind; Yingdong Zhao; Mai-Britt Zocca; Francesco M Marincola Journal: J Transl Med Date: 2009-06-17 Impact factor: 5.531