The genetic association of primary biliary cholangitis with major histocompatibility complex (MHC) has been widely confirmed among different ethnicities. To map specific MHC region variants associated with PBC in a Han Chinese cohort, we imputed HLA antigens and amino acids (AA) in 1126 PBC cases and 1770 healthy control subjects using a Han-MHC reference database. We demonstrate that HLA-DRB1 and/or HLA-DQB1 contributed the strongest signals, and that HLA-DPB1 was a separate independent locus. Regression analyses with classical HLA alleles indicate that HLA-DQB1*03:01 or HLA-DQβ1-Pro55, HLA-DPB1*17:01 or HLA-DPβ1-Asp84 and HLA-DRB1*08:03 could largely explain MHC association with PBC. Forward stepwise regression analyses with HLA amino acid variants localize the major signals to HLA-DRβ1-Ala74, HLA-DQβ1-Pro55 and HLA-DPβ1-Asp84. Electrostatic potential calculations implicated AA variations at HLA-DQβ1 position 55 and HLA-DPβ1 position 84 as critical to peptide binding properties. Furthermore, although several critical Han Chinese AA variants differed from those shown in European populations, the predicted effects on antigen binding are likely to be very similar or identical and underlie the major component of MHC association with PBC.

中文翻译：

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MHC区域的精细定位可确定与汉族原发性胆源性胆管炎有关的主要独立变体。

在不同种族之间，原发性胆源性胆管炎与主要组织相容性复合体（MHC）的遗传关联已得到广泛证实。为了绘制汉族人群中与PBC相关的特定MHC区域变体，我们使用Han-MHC参考数据库估算了1126例PBC病例和1770名健康对照受试者的HLA抗原和氨基酸（AA）。我们证明，HLA-DRB1和/或HLA-DQB1贡献了最强的信号，并且HLA-DPB1是一个独立的独立基因座。使用经典HLA等位基因进行回归分析表明，HLA-DQB1 * 03：01或HLA-DQβ1-Pro55，HLA-DPB1 * 17：01或HLA-DPβ1-Asp84和HLA-DRB1 * 08：03可以在很大程度上解释MHC与PBC的关联。使用HLA氨基酸变体进行的逐步逐步回归分析将主要信号定位于HLA-DRβ1-Ala74，HLA-DQβ1-Pro55和HLA-DPβ1-Asp84。静电势计算暗示HLA-DQβ1位置55和HLA-DPβ1位置84的AA变化对肽结合特性至关重要。此外，尽管几个关键的汉族AA变异与欧洲人群中显示的变异不同，但是对抗原结合的预测作用可能非常相似或相同，并且是MHC与PBC结合的主要组成部分。