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  • Title: Genetic analysis of the HLA region of Japanese patients with type 1 autoimmune hepatitis.
    Author: Yoshizawa K, Ota M, Katsuyama Y, Ichijo T, Matsumoto A, Tanaka E, Kiyosawa K.
    Journal: J Hepatol; 2005 Apr; 42(4):578-84. PubMed ID: 15763345.
    Abstract:
    BACKGROUND/AIMS: Genetic predisposition to type 1 autoimmune hepatitis (AIH) is 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. METHODS: We performed association analysis using HLA class I and II alleles and 18 polymorphic microsatellite markers distributed throughout the HLA region. We specifically assessed tumor necrosis factor (TNF)-alpha gene polymorphisms. RESULTS: The frequencies of HLA-DRB1*0405, DRB4 and DQB1*0401 alleles were significantly 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 segment was located around the HLA-DR/-DQ subregion, the second was around the HLA-B54 allele, and the third was around two microsatellites near the TNF gene cluster. However, stratification analysis for the effect of DRB1*0405 eliminated association of the latter two segments. Haplotype D of the TNF-alpha promoter gene polymorphisms was weakly associated with susceptibility, but was found to be not significant after stratification analysis. CONCLUSIONS: The most influential gene on type 1 AIH pathogenesis in Japanese is the HLA-DRB1. Other genes in the HLA region, including TNF-alpha, have little or no association with type 1 AIH susceptibility.
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