title: Analysis of major histocompatibility complex and CTLA-4 alleles in Brazilian patients with primary biliary cirrhosis.
abstract: OBJECTIVE
  Predisposition to primary biliary cirrhosis (PBC) has been classically linked to HLA-DRB1 locus. However, the presence of the HLA-DRB1*08 antigen has been reported in less than one-third of PBC patients from Northern Europe and Japan. Recently, polymorphisms in the tumor necrosis factor alpha (TNFA) gene promoter at position -308 and in exon 1 of the cytotoxic T lymphocyte antigen-4 (CTLA-4) gene at position 49 have been associated with susceptibility to PBC in Caucasians. In addition, the presence of HLA-DRB1*08 and the TNFA*1 allele was also linked to progression to end-stage liver disease. The aims of the present study were to investigate the frequencies of HLA-DR and DQ antigens and TNFA and CTLA-4 alleles in PBC patients from a different genetic background, as well as to assess the role of TNFA alleles and HLA-DR antigens in disease progression.
  
  
  METHODS
  Determination of HLA-DRB1, DQB1, TNFA and CTLA-4 alleles was performed in patients with PBC and healthy controls using polymerase chain reaction-based techniques.
  
  
  RESULTS
  Frequencies of HLA-DR and DQ antigens were similar in PBC patients and healthy controls. Accordingly, no association between TNFA and CTLA-4 alleles was observed in PBC patients. The histological stage at admission of patients with PBC also showed no correlation with HLA antigens and TNFA and CTLA-4 alleles.
  
  
  CONCLUSIONS
  Susceptibility to PBC in Brazil is not associated with HLA-DR and DQ antigens and CTLA-4 genotypes. TNFA alleles were not shown to influence disease progression.
authors.affiliation: Portuguese Hospital of Salvador, Rua Tamoios 314, Rio Vermelho, Salvador-Bahia, Brazil CEP: 41940-040. plbbr@uol.com.br
authors.forename: Paulo Lisboa
authors.initials: PL
authors.lastname: Bittencourt
authors.forename: Selma Aliotti
authors.initials: SA
authors.lastname: Palácios
authors.forename: Alberto Queiroz
authors.initials: AQ
authors.lastname: Farias
authors.forename: Clarice Pires
authors.initials: CP
authors.lastname: Abrantes-Lemos
authors.forename: Eduardo Luiz Rachid
authors.initials: EL
authors.lastname: Cançado
authors.forename: Flair José
authors.initials: FJ
authors.lastname: Carrilho
authors.forename: Antonio Atílio
authors.initials: AA
authors.lastname: Laudanna
authors.forename: Jorge
authors.initials: J
authors.lastname: Kalil
authors.forename: Anna C
authors.initials: AC
authors.lastname: Goldberg
mesh_terms: D000483:Alleles; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000235:genetics*; D001938:Brazil; D060908:CTLA-4 Antigen; D018450:Disease Progression; D005260:Female; D006683:HLA-DQ Antigens / Q000235:genetics*; D006684:HLA-DR Antigens / Q000235:genetics*; D006801:Humans; D008105:Liver Cirrhosis, Biliary / Q000235:genetics*; D008297:Male; D008875:Middle Aged
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens