Afdhal N, Geahigan T, Brown RS Jr, Dove L, Stovel S, Martin M, Terrault N, Straley S, Agudelo E, Hinds M, Heberlein J, Wiley TE, Williams M, Howell CD, Gibson K, Callison K, Lewis J, Jeffers LJ, Baker SM, DeMedina M, Hermitt C, Conjeevaram HS, Fontana RJ, Harsh D, Fried MW, Smith SR, Theodore D, Zacks S, Shrestha R, Dougherty K, Davis P, Brown S, Tavis JE, Di Bisceglie A, Yao E, Donlin M, Cannon N, Wang P, Yang H, Tang G, Wang D, Rosen HR, Burton JR, Klarquist J, Weston S, Taylor MW, Sanda C, Tsukahara T, Ferris M, Belle SH, Bilonick RA, Block G, Cline J, Haritos M, Im K, Kelley S, Kelsey S, Koozer L, Lawlor S, Thomas SB, Wahed A, Wei Y, Yee LJ, Zhang S, Robuck P, Everhart J, Hoofnagle JH, Doo E, Liang TJ, Seeff LB, Kleiner DE.
Source
Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Abstract
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.