title: Genetic variants in interferon-λ 4 influences HCV clearance in Chinese Han population.
abstract: Recent many studies indicated a novel dinucleotide variant in ss469415590 (TT vs. ΔG) of interferon-λ 4 (IFNL4) gene strongly associated with hepatitis C virus clearance. To evaluate the impact and clinical usefulness of IFNL4 ss469415590 genotype on predicting both spontaneous HCV clearance and response to therapy in Chinese population, we genotyped 795 chronic HCV carriers, 460 subjects with HCV natural clearance and 362 patients with pegylated interferon-α and ribavirin (PEG IFN-α/RBV) treatment. IFNL4 ss469415590 variant genotypes significantly decreased host HCV clearance, both spontaneous (dominant model: OR = 0.50, 95% CI = 0.36-0.71) and IFN-α induced (dominant model: OR = 0.32, 95% CI = 0.18-0.56). Multivariate stepwise analysis indicated that ss469415590, rs12979860, the level of baseline HCV RNA and platelet were as independent predictors for sustained virological response (SVR). But the area under the ROC curve (AUC) was only 0.58 for ss469415590, and it was elevated to 0.71 by adding rs12979860, baseline HCV RNA and platelet in the prediction model of SVR. Therefore, these findings underscore that although genetic factors of host and pathogen were commonly important during HCV clearance, ss469415590 may be also a strongly predictive marker in the Chinese population.
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Huang
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Yinan
authors.initials: Y
authors.lastname: Yao
authors.affiliation: Department of Infectious Diseases, the People's Hospital of Jiangsu Province, Nanjing 210029, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Yue
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Tian
authors.affiliation: Department of Infectious Diseases, the Jurong Peoples' Hospital, Jurong 212400, China.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Mingzhu
authors.initials: M
authors.lastname: Chen
authors.affiliation: School of Nursing, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Wang
authors.affiliation: Huadong Research Institute for Medicine and Biotechnics, No. 293 Zhongshan East Road, Nanjing 210002, Jiangsu, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Rongbin
authors.initials: R
authors.lastname: Yu
mesh_terms: D000328:Adult; D000483:Alleles; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use; D044466:Asian People / Q000235:genetics; D002681:China / Q000453:epidemiology; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics; D006526:Hepatitis C / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics* / Q000821:virology*; D054884:Host-Pathogen Interactions / Q000235:genetics*; D006801:Humans; D007378:Interleukins / Q000235:genetics*; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D012372:ROC Curve; D019562:Viral Load; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D007378:Interleukins; C579163:IFNL4 protein, human; D000095022:Interferon Lambda