title: Novel host genetic variations associated with spontaneous clearance of a single-source outbreak of HCV1b infections.
abstract: OBJECTIVE
  A total of 105 patients were identified as accidentally infected with hepatitis C virus genotype 1b (HCV1b) through blood transfusion from a single blood donor. This group provides a unique patient population to study host factors involved in the spontaneous clearance of HCV and disease progression.
  
  
  METHODS
  Clinical markers, HCV RNA and eight single nucleotide polymorphisms (SNPs) of interleukin-28B (IL-28B) were detected. Exome capture and sequencing were analysed for association with HCV clearance.
  
  
  RESULTS
  Among the 85 patients with the positive HCV antibody, 27 cases (31.8%) were HCV RNA negative over a period of 9-12 years. Of the 58 patients with positive HCV RNA, 22.4% developed chronic hepatitis, and 5.2% developed cirrhosis. Age was found to be associated with HCV1b clearance. IL-28 rs10853728 CC showed the trend. By exon sequencing, 39 SNPs were found to be significantly different in spontaneous clearance patients (p<0.001). Two SNPs in the tenascin receptor (TNR), five in the transmembrane protease serine 11A (TMPRSS11A), and one in the serine peptidase inhibitor kunitz type 2 (SPINT2) showed the closest associations (p<10(-5)).
  
  
  CONCLUSIONS
  Host genetic analyses on the unique, single source HCV1b-infected patient population has suggested that age and mutations in TNR, TMPRSS11A and SPINT2 genes may be factors associated with HCV clearance.
authors.affiliation: Liver Research Center , Beijing Key Laboratory of Translational Medicine in Liver Cirrhosis, Beijing Friendship Hospital, Capital Medical University , Beijing , China.
authors.forename: Hong
authors.initials: H
authors.lastname: You
authors.affiliation: Department of Infectious Diseases , Qiannan People's Hospital , Guizhou , China.
authors.forename: Sandu
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Infectious Diseases , Pingtang People's Hospital , Guizhou , China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Xie
authors.affiliation: Liver Research Center , Beijing Key Laboratory of Translational Medicine in Liver Cirrhosis, Beijing Friendship Hospital, Capital Medical University , Beijing , China.
authors.forename: Rui
authors.initials: R
authors.lastname: Cong
authors.affiliation: Liver Research Center , Beijing Key Laboratory of Translational Medicine in Liver Cirrhosis, Beijing Friendship Hospital, Capital Medical University , Beijing , China.
authors.forename: Yameng
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Beijing Genomic Institute , Shenzhen, Guangdong , China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Ren
authors.affiliation: Beijing Genomic Institute , Shenzhen, Guangdong , China.
authors.forename: Kangfei
authors.initials: K
authors.lastname: Wei
authors.affiliation: Beijing Genomic Institute , Shenzhen, Guangdong , China.
authors.forename: Xin
authors.initials: X
authors.lastname: Jin
authors.affiliation: Beijing Genomic Institute , Shenzhen, Guangdong , China.
authors.forename: Yujian
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Hepatology Institute, Peking University People's Hospital , Beijing , China.
authors.forename: Haiying
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Microbiology , Peking University Health Science Center , Beijing , China.
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.affiliation: Hepatology Institute, Peking University People's Hospital , Beijing , China.
authors.forename: Lai
authors.initials: L
authors.lastname: Wei
authors.affiliation: Department of Microbiology , Peking University Health Science Center , Beijing , China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhuang
authors.affiliation: Department of Infectious Diseases , Guiyang Medical College , Guizhou , China.
authors.forename: Mingliang
authors.initials: M
authors.lastname: Cheng
authors.affiliation: Liver Research Center , Beijing Key Laboratory of Translational Medicine in Liver Cirrhosis, Beijing Friendship Hospital, Capital Medical University , Beijing , China.
authors.forename: Jidong
authors.initials: J
authors.lastname: Jia
keywords: CHRONIC HEPATITIS; GENETICS; HCV