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

Xiaowen Su, Leland J. Yee, KyungAh Im, Shannon L. Rhodes, YongMing Tang, Xiaomei Tong, Charles Howell, Darmendra Ramcharran, Hugo R. Rosen, Milton W. Taylor, T. Jake Liang, Huiying Yang

Research output: Contribution to journalArticlepeer-review

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 α-2a (Peg-IFN-α) 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-nai{dotless}̈ve 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.

Original languageEnglish (US)
Pages (from-to)184-191
Number of pages8
JournalJournal of Hepatology
Volume49
Issue number2
DOIs
StatePublished - Aug 2008
Externally publishedYes

Keywords

  • Genetics
  • Hepatitis C
  • Interferon
  • Interferon signaling pathway genes
  • Interferon therapy
  • Interferon-stimulated genes
  • Pharmacogenetics
  • Race
  • Therapy

ASJC Scopus subject areas

  • Gastroenterology

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