IL28B genetic variations are associated with high sustained virological response (SVR) of interferon-α plus ribavirin therapy in Taiwanese chronic HCV infection

被引:45
作者
Chen, J-Y [2 ]
Lin, C-Y [1 ]
Wang, C-M [3 ]
Lin, Y-T [2 ]
Kuo, S-N [2 ]
Shiu, C-F [4 ]
Chang, S-W [4 ]
Wu, J. [5 ]
Sheen, I-S [1 ]
机构
[1] Chang Gung Univ, Coll Med, Div Gastroenterol & Hepatol, Chang Gung Mem Hosp,Dept Med, Tao Yuan, Taiwan
[2] Chang Gung Univ, Coll Med, Chang Gung Mem Hosp, Div Allergy Immunol & Rheumatol,Dept Med, Tao Yuan, Taiwan
[3] Chang Gung Univ, Coll Med, Chang Gung Mem Hosp, Dept Rehabil, Tao Yuan, Taiwan
[4] Acad Sinica, Inst Biomed Sci, Div Biostat, Taipei, Taiwan
[5] Univ Minnesota, Dept Vet & Biomed Sci, St Paul, MN 55108 USA
关键词
hepatitis C; sustained virological response; IL28B; single-nucleotide polymorphisms; HEPATITIS-C VIRUS; NATURAL-KILLER-CELLS; DENDRITIC CELLS; IMMUNE-RESPONSES; INNATE IMMUNITY; T-CELLS; ANTIVIRAL ACTIVITY; SIGNALING PATHWAY; VIRAL-INFECTION; IFN-LAMBDA;
D O I
10.1038/gene.2011.1
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Chronic hepatitis C virus (HCV) infection patients exhibit different sustained virological responses (SVRs) following the treatment with pegylated interferon-alpha (IFN-alpha) and ribavirin. Genome-wide association studies consistently linked SVR of IFN-alpha-based therapy to the IL28B single-nucleotide polymorphisms (SNPs) on chromosome 19q.13 in various populations. This study was undertaken to investigate the association of IL28B SNPs with SVR in a cohort of Taiwanese chronic HCV patients. Ten SNPs of IL28B were genotyped in 728 chronic HCV patients and 960 healthy controls. Genotype distributions, allele frequencies and haplotypes were tested for SVR and susceptibility in Taiwanese chronic HCV patients. Non-genotype 1 infection (adjusted P = 3.3 x 10(-12), odds ratio (OR) 0.179; 95% confidence interval (CI): 0.110-0.290) and low HCV viral load (<400 000 IU ml(-1)) (adjusted P = 3.5 x 10(-9), OR 0.299; 95% CI: 0.200-0.446) were two major factors identified for high SVR. Notably, eight IL28B SNPs including previously described disease-associated SNPs (Trend test P = 0.005) were significantly associated with SVR. Our data indicate that IL28B polymorphisms are the essential contributing factors for high SVR in Taiwanese chronic HCV patients. Combination of virus genotyping and host genetic data may be used to select the optimal treatment regimes in IFN-based therapy. Genes and Immunity (2011) 12, 300-309; doi:10.1038/gene.2011.1; published online 24 February 2011
引用
收藏
页码:300 / 309
页数:10
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