title: Association of HLA-DP/DQ, STAT4 and IL-28B variants with HBV viral clearance in Tibetans and Uygurs in China.
abstract: OBJECTIVE
  Several genome-wide association studies have revealed that HLA-DP/DQ, STAT4 and IL-28B associated with liver diseases. But because of population heterogeneity, different races would have different causative polymorphisms. Therefore, in this study, we included Chinese Tibetans and Uygurs to examine the roles of these genes on HBV natural clearance.
  
  
  METHODS
  A total of 1341 subjects including 908 Tibetans and 433 Uygurs were recruited. Seven single nucleotide polymorphisms (SNP) were genotyped.
  
  
  RESULTS
  HLA-DP/DQ polymorphisms associated with HBV natural clearance in both ethnicities (Tibetans, rs3077, OR = 0.61, 95% CI = 0.46-0.82; rs9277535, OR = 0.56, 95% CI = 0.41-0.75; rs7453920, OR = 0.64, 95%CI = 0.47-0.85; Uygurs, rs3077, OR = 0.48, 95% CI = 0.24-0.96; rs9277535, OR = 0.43, 95% CI = 0.20-0.91; rs7453920, OR = 0.62, 95% CI = 0.39-0.99), whereas no significant association was observed between IL-28B with HBV natural clearance in neither ethnicities (P > 0.05). STAT4 rs7574865 seemed to be Tibetan specific in HBV natural clearance (OR = 0.76, 95% CI = 0.58-0.99). Moreover, in Tibetan patients, HLA-DQ rs7453920 GG had a higher frequency in HBeAg positive patients (P = 0.032) and STAT4 rs7574865 GG genotype appeared more frequently in Genotype C virus infected patients (P = 0.005). In addition, Uygurs have higher frequencies of HLA-DP/DQ protective alleles (72.5% for rs3077, 76.6% for rs9277535 and 26.8% for rs7453920) than Tibetans (51.7% for rs3077, 52.5% for rs9277535 and 18.5% for rs7453920)(all P < 0.05), and a lower prevalence of HBV infection as previously reported.
  
  
  CONCLUSIONS
  HLA-DP/DQ but not IL-28B polymorphisms correlate with HBV natural clearance, irrespective of race, and HLA-DP/DQ would be causative genes attributing to varying prevalence in different regions. STAT4 rs7574865 seemed to be population specific in Tibetans and it might synergistically interact with virus contributing to disease progression.
authors.affiliation: Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, 610041, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Liao
authors.forename: Bei
authors.initials: B
authors.lastname: Cai
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.forename: Binwu
authors.initials: B
authors.lastname: Ying
authors.forename: Chuanmin
authors.initials: C
authors.lastname: Tao
authors.forename: Min
authors.initials: M
authors.lastname: Zhao
authors.forename: Zhu
authors.initials: Z
authors.lastname: Ba
authors.forename: Zhaoxia
authors.initials: Z
authors.lastname: Zhang
authors.forename: Lanlan
authors.initials: L
authors.lastname: Wang
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D002681:China; D005260:Female; D005787:Gene Frequency; D006682:HLA-DP Antigens / Q000235:genetics*; D006683:HLA-DQ Antigens / Q000235:genetics*; D006239:Haplotypes; D006509:Hepatitis B / Q000235:genetics* / Q000276:immunology / Q000821:virology; D006513:Hepatitis B e Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000235:genetics; D006801:Humans; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D050797:STAT4 Transcription Factor / Q000235:genetics*; D018609:Tibet / Q000208:ethnology; D019562:Viral Load; D055815:Young Adult; D000095022:Interferon Lambda
chemical_list: D006682:HLA-DP Antigens; D006683:HLA-DQ Antigens; D006513:Hepatitis B e Antigens; D007372:Interferons; D007378:Interleukins; D050797:STAT4 Transcription Factor; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C494090:STAT4 protein, human
keywords: HBV; HLA-DP/DQ; IL-28B; STAT4; Tibetan; Uygur