Association of single nucleotide polymorphisms in interferon signaling pathway genes and interferon-stimulated genes with the response to interferon therapy for chronic hepatitis C

Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Journal of Hepatology (Impact Factor: 11.34). 09/2008; 49(2):184-91. DOI: 10.1016/j.jhep.2008.04.011
Source: PubMed


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.
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.
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.
Our study suggests that OASL variants are involved in the host response to IFN-based therapy in HCV patients.

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Available from: Yongming Tang, Mar 18, 2015
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    • "= suppressor of cytokine signalling 3. Underlined HLA alleles appear in more than one study. References: (Thio, Gao et al. 2002; McKiernan, Hagan et al. 2004; Wang, Zheng et al. 2009), (Thio, Thomas et al. 2001; Yee 2004; Yoon, Han et al. 2005; Ksiaa, Ayed-Jendoubi et al. 2007; Harris, Sugimoto et al. 2008), (Ishida, Ikebuchi et al. 2011), (Falleti, Fabris et al. 2010), (Haas, Weiß et al. 2009), (Mueller, Mas-Marques et al. 2004), (Yee, Tang et al. 2001) (Morgan, Lambrecht et al. 2008), (Thio, Goedert et al. 2004; Paladino, Fainboim et al. 2006), (Knapp, Hennig et al. 2003; Lio, Caruso et al. 2003; Kimura, Saito et al. 2006; An, Thio et al. 2008), (Schott, Witt et al. 2008), (Huang, Yang et al. 2007), (Ge, Fellay et al. 2009; Mangia, Thompson et al. 2010), (Tanaka, Nishida et al. 2009; Rauch, Kutalik et al. 2010), (Vejbaesya, Nonnoi et al. 2011), (Khakoo, Thio et al. 2004; Montes-Cano, Caro-Oleas et al. 2005), (Persico, Capasso et al. 2008), (Su, Yee et al. 2008), (Suzuki, Arase et al. 2004), (Knapp, Yee et al. 2003), (Dai, Chuang et al. 2010). "

    Analysis of Genetic Variation in Animals, 02/2012; , ISBN: 978-953-51-0093-5
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    • "The molecular mechanisms of IFN-α resistance are unclear, however a number of studies have provided evidence that both viral and cellular factors are involved [18-23]. We provided evidence that replicon cells develop IFN-α resistance due to defective Jak-Stat signaling. "
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    • "Also, the sequencing of the human genome will offer unique opportunities and genome-wide association studies will help us better target antiviral therapy to individual patients, particularly in patients with difficultto-treat patient groups. For example, basal levels of SOCS3, an inhibitor of the IFN alphainduced Janus kinase-signal transducer and its genetic polymorphisms influence the outcome of antiviral treatment [Su et al. 2008]. Su et al. also reported that in a cohort of genotype-1 patients, single nucleotide polymorphisms in interferon signaling pathway genes and IFNstimulated genes was associated with SVR [Persico et al. 2007]. "
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