Linkage disequilibrium between HLA class II region and autoimmune hepatitis in pediatric patients

Abstract Background/Aims Susceptibility HLA class II alleles associated with autoimmune hepatitis (AIH) were only described in case-control studies. Methods The transmission/disequilibrium test was used in 50 simplex families with AIH, to determine if affected offspring received the disease-associated allele more frequently than its alternate. HLA-DRB1 and DQB1 allele genotyping and autoimmune regulator (AIRE) polymorphisms located in exons 6, 8 and 10 were investigated by PCR-based methods. Results HLA-DRB1*03 allele was significantly transmitted from heterozygous parent to affected offspring (81.5%) with type 1 AIH compared to random expected frequency (50.0%; P =0.004) or to unaffected offspring (42.8%; P =0.03). HLA-DRB1*1301 allele showed an excess transmission to affected children (100%) than expected frequency ( P P =0.001). The transmission of DQB1*201 or DQB1*0603 alleles showed significant deviation in patients compared to random frequencies: (84.8%; P P P =0.0005). Conclusions HLA-DRB1 gene is the major genetic determinant in HLA class II region for children with type 1 AIH. Type 2 AIH is associated with the HLA-DQB1gene. Finally, AIRE gene abnormality does not contribute to the development of isolated AIH.