title: A novel polymorphism near HLA class II region is associated with spontaneous clearance of HCV and response to interferon treatment in Chinese patients.
abstract: A recent genome-wide association study (GWAS) has identified the single-nucleotide polymorphism (SNP) rs4273729 in a 100-kbp region comprising human leukocyte antigens (HLAs) class II genes as an important predictor of hepatitis C virus (HCV) clearance in European and African populations. This study was to determine whether this polymorphism is also associated with spontaneous HCV clearance as well as response to interferon treatment in Chinese patients. Thus, 686 chronic HCV carriers, 432 individuals with spontaneous viral clearance and 243 patients with pegylated interferon-α and ribavirin (PEG IFN-α/RBV) treatment were genotyped. The rs4273729 GG genotype was strongly associated with spontaneous HCV clearance as well as better IFN/RBV treatment response compared with the GC/CC genotypes in Chinese Han population (additive model: odds ratio (OR)=0.62, 95% confidence interval (95% CI)=0.51-0.76; OR=0.58, 95% CI=0.38-0.88, respectively). Rs4273729, rs12980275, baseline HCV RNA and platelet level were independent predictors for sustained virological response (SVR). The area under the receiver-operating characteristic curve (AUC) was 0.578 when including rs4273729 alone, but the prediction value was improved significantly (AUC=0.733) when further including rs12980275, baseline viral load and baseline platelet level. In conclusion, the genetic variation of rs4273729 is associated with clearance of HCV in both the natural course and the treatment process in Chinese Han population.
authors.affiliation: Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Yin
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Huang
authors.affiliation: Department of Infectious Diseases, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Yue
authors.affiliation: Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Su
authors.affiliation: Department of Infectious Diseases, The Jurong People's Hospital, Jurong, China.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Mingzhu
authors.initials: M
authors.lastname: Chen
authors.affiliation: Department of Basic and Community Nursing, School of Nursing, Nanjing Medical University, Nanjing, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Infectious Diseases, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Zhihang
authors.initials: Z
authors.lastname: Peng
authors.affiliation: Institute of Epidemiology and Microbiology, Huadong Research Institute for Medicine and Biotechnics, Nanjing, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Rongbin
authors.initials: R
authors.lastname: Yu
mesh_terms: D000368:Aged; D044466:Asian People; D054316:Biomarkers, Pharmacological; D005260:Female; D005838:Genotype; D006680:HLA Antigens / Q000235:genetics*; D016174:Hepacivirus / Q000235:genetics* / Q000472:pathogenicity; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012254:Ribavirin / Q000008:administration & dosage; D016896:Treatment Outcome; D019562:Viral Load / Q000235:genetics
chemical_list: D054316:Biomarkers, Pharmacological; D006680:HLA Antigens; D016898:Interferon-alpha; D012254:Ribavirin