cqvip:Background/Aims: Genetic predisposition to type 1 autoimmune hepatitis (AIH) i s linked mainly to HLA-class II genes.The aim of this study is to scan the HLA region for additional genes which may contribute to type 1 AIH susceptibility. M ethods:We performed association analysis using HLA class I and II alleles and 18 polymorphic microsatellite markers distributed throughout the HLA region. We sp ecifically assessed tumor necrosis factor (TNF)-αgene polymorphisms. Results: The frequencies of HLA-DRB1*0405, DRB4 and DQB1*0401 alleles were significant ly higher in AIH patients. The association study revealed the presence of three segments in the HLA region showing significantly low P (Pc) values. The first se gment was located around the HLA-DR/-DQ subregion, the second was around the H LA-B54 allele, and the third was around two microsatellites near the TNF gene c luster. However, stratification analysis for the effect of DRB1*0405 eliminated association of the latter two segments. Haplotype D of the TNF-αpromoter gene polymorphisms was weakly associated with susceptibility,but was found to be not significant after stratification analysis.Conclusions: The most influential gen e on type 1 AIH pathogenesis in Japanese is the HLA-DRB1. Other genes in the HL A region, including TNF-α, have little or no associationwith type 1 AIH suscep tibility.
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