title: Association of T-cell immunoglobulin and mucin domain-containing molecule 3 (Tim-3) polymorphisms with susceptibility and disease progression of HBV infection.
abstract: OBJECTIVE
  T-cell immunoglobulin and mucin domain-containing molecule 3 (Tim-3) plays an important role in regulating T cells in hepatitis B virus (HBV) infection and hepatocellular carcinoma (HCC). However, few researches have reported the association of Tim-3 genetic variants with susceptibility and progression of HBV infection. In this study, we focused on the association of Tim-3 polymorphisms with HBV infection, HBsAg seroclearance and hepatocellular carcinoma.
  
  
  METHODS
  A total of 800 subjects were involved in this study. Four groups were studied here, including HBV, HBsAg seroclearance, HBV-associated HCC and healthy controls. Three single-nucleotide polymorphisms (SNPs) of Tim-3, rs246871, rs25855 and rs31223 were genotyped to analyze the association of Tim-3 polymorphisms with susceptibility and disease progression of HBV infection.
  
  
  RESULTS
  Our study found that rs31223 and rs246871 were associated with disease progression of HBV infection, while none of the three SNPs was relevant to HBV susceptibility. The minor allele "C" of rs31223 was found to be associated with an increased probability of HBsAg seroclearance (P = 0.033) and genotype "CC" of rs246871 to be associated with an increased probability of HBV-associated HCC (P = 0.007). In accordance, haplotypic analysis of the three polymorphisms also showed that the haplotype block CGC* and TGC* were significantly associated with HBsAg seroclearance (P<0.05) while haplotype block CAT*, CGT*, TAC* and TGT* were significantly associated with HBV-associated HCC (all P<0.05).
  
  
  CONCLUSIONS
  Genetic variants of Tim-3 have an important impact on disease progression of HBV infection. With specific Tim-3 polymorphisms, patients infected with HBV could be potential candidates of HCC and HBsAg seroclearance.
authors.affiliation: Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Jingyu
authors.initials: J
authors.lastname: Liao
authors.affiliation: Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Liao
authors.affiliation: Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Bei
authors.initials: B
authors.lastname: Cai
authors.affiliation: Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Lixin
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Lanlan
authors.initials: L
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000150:complications* / Q000235:genetics / Q000821:virology; D016022:Case-Control Studies; D018450:Disease Progression; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D000072597:Hepatitis A Virus Cellular Receptor 2; D006509:Hepatitis B / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D006514:Hepatitis B Surface Antigens / Q000276:immunology; D006515:Hepatitis B virus / Q000502:physiology*; D006801:Humans; D008113:Liver Neoplasms / Q000150:complications* / Q000235:genetics / Q000821:virology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: C448908:HAVCR2 protein, human; D000072597:Hepatitis A Virus Cellular Receptor 2; D006514:Hepatitis B Surface Antigens; D008565:Membrane Proteins