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 journalArticle

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

Fingerprint

Chronic Hepatitis C
Interferons
Single Nucleotide Polymorphism
Hepacivirus
Genes
Therapeutics
Ribavirin
Virus Diseases
Genotype
Sustained Virologic Response

Keywords

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

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Association of single nucleotide polymorphisms in interferon signaling pathway genes and interferon-stimulated genes with the response to interferon therapy for chronic hepatitis C. / Su, Xiaowen; Yee, Leland J.; Im, KyungAh; Rhodes, Shannon L.; Tang, YongMing; Tong, Xiaomei; Howell, Charles; Ramcharran, Darmendra; Rosen, Hugo R.; Taylor, Milton W.; Liang, T. Jake; Yang, Huiying.

In: Journal of Hepatology, Vol. 49, No. 2, 08.2008, p. 184-191.

Research output: Contribution to journalArticle

Su, X, Yee, LJ, Im, K, Rhodes, SL, Tang, Y, Tong, X, Howell, C, Ramcharran, D, Rosen, HR, Taylor, MW, Liang, TJ & Yang, H 2008, 'Association of single nucleotide polymorphisms in interferon signaling pathway genes and interferon-stimulated genes with the response to interferon therapy for chronic hepatitis C', Journal of Hepatology, vol. 49, no. 2, pp. 184-191. https://doi.org/10.1016/j.jhep.2008.04.011
Su, Xiaowen ; Yee, Leland J. ; Im, KyungAh ; Rhodes, Shannon L. ; Tang, YongMing ; Tong, Xiaomei ; Howell, Charles ; Ramcharran, Darmendra ; Rosen, Hugo R. ; Taylor, Milton W. ; Liang, T. Jake ; Yang, Huiying. / Association of single nucleotide polymorphisms in interferon signaling pathway genes and interferon-stimulated genes with the response to interferon therapy for chronic hepatitis C. In: Journal of Hepatology. 2008 ; Vol. 49, No. 2. pp. 184-191.
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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.",
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T1 - Association of single nucleotide polymorphisms in interferon signaling pathway genes and interferon-stimulated genes with the response to interferon therapy for chronic hepatitis C

AU - Su, Xiaowen

AU - Yee, Leland J.

AU - Im, KyungAh

AU - Rhodes, Shannon L.

AU - Tang, YongMing

AU - Tong, Xiaomei

AU - Howell, Charles

AU - Ramcharran, Darmendra

AU - Rosen, Hugo R.

AU - Taylor, Milton W.

AU - Liang, T. Jake

AU - Yang, Huiying

PY - 2008/8

Y1 - 2008/8

N2 - 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.

AB - 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.

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KW - Interferon

KW - Interferon signaling pathway genes

KW - Interferon therapy

KW - Interferon-stimulated genes

KW - Pharmacogenetics

KW - Race

KW - Therapy

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