title: Polymorphisms in CISH gene are associated with persistent hepatitis B virus infection in Han Chinese population.
abstract: OBJECTIVE
  Cytokine-inducible SRC homology 2 domain protein (CISH) is the first member of the suppressors of cytokine signaling (SOCS) protein family. An association between multiple CISH polymorphisms and susceptibility to infectious diseases has been reported. This study aimed to investigate the possible association of these single nucleotide polymorphisms (SNPs) in CISH gene with different outcomes of Hepatitis B virus (HBV) infection.
  
  
  METHODS
  1019 unrelated Chinese Han subjects, including 240 persistent asymptomatic HBV carriers, 217 chronic hepatitis B patients, 137 HBV-related liver cirrhosis patients, and 425 cases of spontaneously recovered HBV as controls, were studied. Four SNPs (rs622502, rs2239751, rs414171 and rs6768300) in CISH gene were genotyped with the snapshot technique. Transcriptional activity of the CISH promoter was assayed in vitro using the dual-luciferase reporter assay system.
  
  
  RESULTS
  At position rs414171, A allele and AA genotype frequencies were significantly higher in the HBV-resolved group as compared to the persistent HBV infection group. At position rs2239751, TT genotype was further observed in the HBV-resolved group. Using asymptomatic HBV carriers as controls, our results indicated that the rs414171 and rs2239751 polymorphisms were unrelated to HBV progression. The other two SNPs (rs622502 and rs6768300) showed no association with persistent HBV infection. Haplotype analysis revealed that the GGCA haplotype was associated with spontaneous clearance of HBV in this population. Moreover, luciferase activity was significantly higher in the PGL3-Basic-rs414171T construct as compared to the PGL3-Basic-rs414171A construct (p<0.001).
  
  
  CONCLUSIONS
  Two SNPs (rs414171 and rs2239751) in the CISH gene were associated with persistent HBV infection in Han Chinese population, but not with HBV progression.
authors: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, China; Department of Infection Disease, The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan Province, China.
authors: Zhangyong
authors: Z
authors: Hu
authors: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, China.
authors: Jinliang
authors: J
authors: Yang
authors: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, China.
authors: Yangping
authors: Y
authors: Wu
authors: Department of Infection Disease, The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan Province, China.
authors: Guolian
authors: G
authors: Xiong
authors: Department of Infection Disease, The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan Province, China.
authors: Yali
authors: Y
authors: Wang
authors: Department of Infection Disease, The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan Province, China.
authors: Jun
authors: J
authors: Yang
authors: Department of Infection Disease, The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan Province, China.
authors: Lan
authors: L
authors: Deng
mesh_terms: D000328:Adult; D044466:Asian People / Q000208:ethnology* / Q000235:genetics; D005006:Ethnicity / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006239:Haplotypes; D019694:Hepatitis B, Chronic / Q000208:ethnology* / Q000235:genetics*; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: D050826:Suppressor of Cytokine Signaling Proteins