title: Genetic contribution of major histocompatibility complex class II region to type 1 autoimmune hepatitis susceptibility in Venezuela.
abstract: OBJECTIVE
  Autoimmune hepatitis (AIH) is a progressive liver disease characterized by the presence of circulating autoantibodies, hypergammaglobulinaemia and a favourable response to immunosuppressive treatment. Although the pathogenesis of type 1 AIH is unknown, disease susceptibility is partially determined by genes linked to the class II region of the major histocompatibility complex. Type 1 AIH has been associated with DRB1*03, DRB1*04 and DRB3 alleles in European and North American Caucasians, with DRB1*0405 in Japanese, with DRB1*0404 in Mexican, and with DRB1*1301 in Argentinean populations.
  
  
  METHODS
  To analyse the molecular basis of these associations in Venezuela (mestizo population), we examined the frequency of human leucocyte antigens (HLA)-A -B -C, HLA-DQ and HLA-DR genes by low- and high-resolution oligonucleotide typing in a population of 41 type 1 AIH patients and 111 ethnic- and aged-matched healthy subjects.
  
  
  RESULTS
  The frequencies of both DRB1(*)1301 (P<0.0001) and DRB1*0301 (P<0.005) were significantly higher in patients than in controls. In addition, patients showed a strong association with the DRB3 allele (P<0.01). In contrast, the DQB1*04 allele was significantly decreased in the patient group (P<0.01). The frequencies of haplotypes A*01-B*08-DQB1*02-DRB1*03-DRB3, DQB1*05-DRB1*1301, DQB1*06-DRB1*1301 and A*02-DRB1*1301, B*45-DRB3 were significantly increased in type 1 AIH patients compared with the controls (P<0.01).
  
  
  CONCLUSIONS
  In conclusion, our data indicate that type 1 AIH predisposition in a Venezuelan mestizo population of different ethnic backgrounds is associated with DRB1*1301 and DRB1*0301 alleles. In addition, our findings suggest that protection against disease might be conferred by the DQB1*04 allele, with distinct ethnic differences from other populations.
authors.affiliation: Institute of Immunology, Universidad Central de Venezuela, Caracas, Venezuela.
authors.forename: María del Pilar
authors.initials: Mdel P
authors.lastname: Fortes
authors.forename: Irma V
authors.initials: IV
authors.lastname: Machado
authors.forename: Gisselle
authors.initials: G
authors.lastname: Gil
authors.forename: Mercedes
authors.initials: M
authors.lastname: Fernández-Mestre
authors.forename: Lucy
authors.initials: L
authors.lastname: Dagher
authors.forename: Roberto V
authors.initials: RV
authors.lastname: León
authors.forename: Nicolás E
authors.initials: NE
authors.lastname: Bianco
authors.forename: Paolo
authors.initials: P
authors.lastname: Tassinari
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000097:blood; D002648:Child; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000208:ethnology; D006239:Haplotypes; D019693:Hepatitis, Autoimmune / Q000208:ethnology / Q000235:genetics* / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D007199:Indians, South American / Q000235:genetics* / Q000706:statistics & numerical data; D008103:Liver Cirrhosis / Q000235:genetics / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D014687:Venezuela / Q000453:epidemiology
chemical_list: D001323:Autoantibodies; D000949:Histocompatibility Antigens Class II