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

• Published in: Journal of hepatology Vol. 49; no. 2; pp. 184 - 191
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier B.V 01.08.2008; Elsevier
• Subjects: Antiviral Agents - metabolism; Antiviral Agents - therapeutic use; Biological and medical sciences; Cohort Studies; Databases, Genetic; Female; Gastroenterology and Hepatology; Gastroenterology. Liver. Pancreas. Abdomen; Gene Frequency; Genetics; Genotype; Hepatitis C; Hepatitis C, Chronic - drug therapy; Hepatitis C, Chronic - epidemiology; Hepatitis C, Chronic - genetics; Human viral diseases; Humans; Infectious diseases; Interferon; Interferon alpha-2; Interferon signaling pathway genes; Interferon therapy; Interferon-alpha - metabolism; Interferon-alpha - therapeutic use; Interferon-stimulated genes; Interferons - genetics; Interferons - metabolism; Male; Medical sciences; Middle Aged; Pharmacogenetics; Polyethylene Glycols - metabolism; Polyethylene Glycols - therapeutic use; Polymorphism, Single Nucleotide; Race; Recombinant Proteins; Regression Analysis; Risk Factors; Signal Transduction - drug effects; Signal Transduction - genetics; Therapy; Viral diseases; Viral hepatitis; AA; Therapy; Pharmacogenetics; Interferon therapy; Interferon signaling pathway genes; Interferon-stimulated genes; SVR; Race; Genetics; HCV; Interferon; Hepatitis C; CA; African Americans; Caucasian Americans; sustained viralogic response; hepatitis C virus; Cytokine; Hepatic disease; Epidemiology; Infection; Treatment; Viral disease; Gastroenterology; Digestive diseases; Single nucleotide polymorphism; Viral hepatitis C
• ISSN: 0168-8278; 1600-0641
• DOI: 10.1016/j.jhep.2008.04.011

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. 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-naı¨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. 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. Our study suggests that OASL variants are involved in the host response to IFN-based therapy in HCV patients.