Article

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: 10.4). 09/2008; 49(2):184-91. DOI: 10.1016/j.jhep.2008.04.011
Source: PubMed

ABSTRACT 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.

Full-text

Available from: Yongming Tang, Mar 18, 2015
0 Followers
 · 
134 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: The prevalence of hepatitis C virus (HCV) infection varies across the world, with the highest percent of infections reported in Middle East, increasingly in Egypt. The current study aimed at examining the bio-statistical correlation and multiple regression analyses of pituitary growth hormone (GH) and liver activities among HCV genotype-4 patients treated with PEG-IFN-α plus RBV therapy. Herein, the current study was conducted on 100 HCV genotype-4 infected patients and 50 healthy controls. Patients received PEG-IFN-α/RBV for 24 weeks. Host RNA was isolated from patients’ sera for HCV genotyping and viral load determination. Moreover, the enzymatic activities of the liver, AFP, GH, PT, and CBC were performed in all volunteers. The present study resulted that the activities of the hepatic enzymes among HCV genotype-4 patients correlated together significantly. While, human GH showed a significant positive regression with pre-treatment ALT concentration in responders. Furthermore, multiple regression analysis for GH showed a significant positive correlation with pre-treatment ALT in HCV genotype-4 infected patients. We concluded that there were a putative significant relation between GH and pre-treatment ALT activity in HCV infection and response to IFN-based therapy.
    Indian Journal of Clinical Biochemistry 10/2013; DOI:10.1007/s12291-013-0309-0
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The study of antiviral pathways to reveal methods for the effective response and clearance of virus is closely related to understanding interferon (IFN) signaling and its downstream target genes, IFN-stimulated genes. One of the key antiviral factors induced by IFNs, 2'-5' oligoadenylate synthase (OAS), is a well-known molecule that regulates the early phase of viral infection by degrading viral RNA in combination with RNase L, resulting in the inhibition of viral replication. In this review, we describe OAS family proteins from a different point of view from that of previous reviews. We discuss not only RNase L-dependent (canonical) and -independent (noncanonical) pathways but also the possibility of the OAS family members as biomarkers for various diseases and clues to non-immunological functions based on recent studies. In particular, we focus on OASL, a member of the OAS family that is relatively less well understood than the other members. We will explain its anti- and pro-viral dual roles as well as the diseases related to single-nucleotide polymorphisms in the corresponding gene.
    Experimental and Molecular Medicine 03/2015; 47(3):e144. DOI:10.1038/emm.2014.110 · 2.46 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Abstract The interferons (IFNs) form part of the large family of glycoproteins known as cytokines. They are secreted by host cells as a line of defence against pathogens and certain tumours. IFNs affect cell proliferation and differentiation and also play a very important role in the functioning of the immune system. Miscarriage in both humans has been associated with higher levels of IFN, particularly IFN-γ. However, this cytokine is evidently vital in successful murine pregnancies since it is involved in maintaining the decidual layer in addition to remodelling of the vasculature in the uterus. The effects of IFN on human pregnancies are more difficult to study. Hence, there is still a lot more to be discovered in the hope of reaching a definite conclusion regarding the impact of IFN.
    Gynecological Endocrinology 11/2013; 30(1). DOI:10.3109/09513590.2012.743011 · 1.14 Impact Factor