AIMS

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 DRB103, DRB104 and DRB3 alleles in European and North American Caucasians, with DRB10405 in Japanese, with DRB10404 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 DRB10301 (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 DQB104 allele was significantly decreased in the patient group (P<0.01). The frequencies of haplotypes A01-B08-DQB102-DRB103-DRB3, DQB105-DRB11301, DQB106-DRB11301 and A02-DRB11301, B45-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 DRB11301 and DRB10301 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.