A functional SNP of interferon-γ gene is important for interferon-α-induced and spontaneous recovery from hepatitis C virus infection

Ying Huang, Huiying Yang, Brian B. Borg, Xiaowen Su, Shannon L. Rhodes, Kai Yang, Xiaomei Tong, George Tang, Charles D. Howell, Hugo R. Rosen, Chloe L. Thio, David L. Thomas, Harvey J. Alter, Ronda K. Sapp, T. Jake Liang

Research output: Contribution to journalArticlepeer-review

Abstract

Cytokine polymorphisms are associated with disease outcome and interferon (IFN) treatment response in hepatitis C virus (HCV) infection. We genotyped eight SNPs spanning the entire IFN-γ gene in two cohorts and assessed the association between those polymorphisms and treatment response or spontaneous viral clearance. The first cohort was composed of 284 chronically HCV-infected patients who had received IFN-α-based therapy and the second was 251 i.v. drug users who had either spontaneously cleared HCV or become chronically infected. A SNP variant located in the proximal IFN-γ promoter region next to the binding motif of heat shock transcription factor (HSF), -764G, was significantly associated with sustained virological response [P = 0.04, odds ratio (OR) = 3.51 (confidence interval 1.0-12.5)]. The association was independently significant in multiple logistic regression (P = 0.04) along with race, viral titer, and genotype. This variant was also significantly associated with spontaneous recovery [P = 0.04, OR = 3.51 (1.0-12.5)] in the second cohort. Functional analyses show that the G allele confers a two- to three-fold higher promoter activity and stronger binding affinity to HSF1 than the C allele. Our study suggests that the IFN-γ promoter SNP -764G/C is functionally important in determining viral clearance and treatment response in HCV-infected patients and may be used as a genetic marker to predict sustained virological response in HCV-infected patients.

Original languageEnglish (US)
Pages (from-to)985-990
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number3
DOIs
StatePublished - Jan 16 2007

Keywords

  • Antiviral treatment
  • Cytokine
  • Genetics
  • Human study
  • Viral clearance

ASJC Scopus subject areas

  • General

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