Genetic contribution of major histocompatibility complex class II region to type 1 autoimmune hepatitis susceptibility in Venezuela

Abstract

AbstractAims: 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.

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