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

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 spontaneou...

Full description

Saved in:

Bibliographic Details
Published in:	Proceedings of the National Academy of Sciences - PNAS 2007-01, Vol.104 (3), p.985-990
Main Authors:	Huang, Ying, Yang, Huiying, Borg, Brian B, Su, Xiaowen, Rhodes, Shannon L, Yang, Kai, Tong, Xiaomei, Tang, George, Howell, Charles D, Rosen, Hugo R, Thio, Chloe L, Thomas, David L, Alter, Harvey J, Sapp, Ronda K, Liang, T. Jake
Format:	Article
Language:	eng
Subjects:	Alleles Base Sequence Biological Sciences Carrier frequencies Cytokines Female Fibrosis Genes Genotype Genotypes Hepatitis C - drug therapy Hepatitis C - genetics Hepatitis C virus Histology Humans Infections Interferon-alpha - therapeutic use Interferon-gamma - genetics Male Middle Aged Molecular Sequence Data Oligonucleotide probes Polymorphism, Single Nucleotide - genetics Promoter regions Promoter Regions, Genetic - genetics T lymphocytes
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	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.
ISSN:	0027-8424 1091-6490