原发性胆汁性肝硬化患者人类白细胞抗原等位基因多态性分析

目的探讨原发性胆汁性肝硬化(PBC)患者人群与人类白细胞抗原(HLA)Ⅰ类(A、B)、Ⅱ类(DRB1)等位基因的相关性,同时评估易感基因是否与一些临床及实验室特征存在联系。方法利用序列特异性聚合酶链反应(SSP-PCR)对65例确诊的PBC患者和431名健康人进行HLA—A、B和DRB1 等位基因以及有关基因亚型分析。结果PBC患者DRB1*07的频率增高到29.2%,与正常人13.9%的频率相比,差异具有统计学意义(Pc<0.05,OR=2.55,95%CI:1.4～4.6);所有DRB1*07阳性患者经亚型分析均为DRB1*0701。未发现DRB1*08与PBC有关联性。Ⅰ类抗原中以A*2在PBC患者组的频率最高(53.8%),稍高于对照组,但无统计学意义。其余HLA-A、B和DRB1的等位基因频率与正常人相比较,差异无统计学意义。DRB1*0701阳性患者与阴性患者在一些临床、实验室指标上差异并不明显。结论PBC与HLA-DRB1*0701基因相关,与南美、北美、北欧、日本等其他国家PBC患者的易感基因明显不同;HLA-DRβ1第78位上的缬氨酸残基可能与PBC发病相关。

Analysis of HLA alleles polymorphism in Chinese patients with primary biliary cirrhosis

OBJECTIVE: To investigate the frequencies of human leuckocyte antigens (HLA) -A, B and DRB1 alleles in Chinese patients with primary biliary cirrhosis (PBC) using polymerase chain reaction-based techniques, and to assess the correlation of HLA molecules with other clinical and laboratory profiles. METHODS: Genotyping of HLA-A, B, and DRB1 were performed in 65 well-characterized patients with primary biliary cirrhosis and 431 healthy controls with PCR amplification with sequence-specific primers (PCR-SSP). RESULTS: The frequency of DRB1*0701 was increased to 29.2% compared with 13.9% in the controls (PC < 0.05, OR = 2.55, 95% CI: 1.4 approximately 4.6). No association was found with HLA-DRB1*08 which had been constantly reported. The A*2 allele (53.8%) was more frequent in the PBC patient group but without a significant statistical difference. The frequencies for the other A, B and DRB1 alleles were similar between patients and healthy controls. There was no difference between patients with or without DRB1*0701 in some clinical and laboratory profiles. CONCLUSION: Susceptibility to primary biliary cirrhosis in Chinese is associated with DRB1*0701 allele and differs from people in North America, South America, North Europe and even in Japan, but the association is not restricted to any particular subgroup of patients. Valine at position 78 of HLA DRbeta1 may play an important role in the pathogenesis of primary biliary cirrhosis.