原发性胆汁性肝硬化患者HLA-Ⅰ类基因的高分辨多态性及单体型分析

HLA class Ⅰ alleles and haplotypes in Chinese patients with primary biliary cirrhosis

目的 分析原发性胆汁性肝硬化（PBC）患者人类白细胞抗原（HLA）Ⅰ类等位基因的高分辨多态性及单体型特征. 方法 采用基于序列测定的聚合酶链反应技术（SBT-PCR）对146例PBC患者和500例健康对照者进行HLA-Ⅰ类基因高分辨分型,比较Ⅰ类基因及单体型在PBC患者和健康对照者间的差异.对PBC患者与健康对照者的基因频率进行x2检验或Fisher精确检验. 结果 PBC患者HLA-A、B、C座位分别检出26、51和21个等位基因,其分布频率在PBC患者和健康对照者间,差异无统计学意义（Pc＞0.05）;PBC患者A＊11：01-B＊40：06和A ＊02：01-B＊15：01单体型频率明显高于健康对照者（7.53％对比1.40％,P＜0.01,OR=5.38;6.85％对比2.00％,P=0.003,OR=3.425）. 结论 PBC患者有独特的HLA-A＊-B＊单体型,可能与疾病遗传易感性相关.

Objective To analyze the HLA class Ⅰ alleles and haplotypes in Chinese patients with primary biliary cirrhosis （PBC）.Methods Sequencing based typing-polymerase chain reaction （SBT-PCR） was used to investigate the HLA class Ⅰ alleles of 146 PBC patients and 500 normal controls in northern China.The frequencies of alleles and haplotypes were calculated and compared for the two groups.The chi-square test and Fisher＇s exact test were used for statistical analyses.Results There were 26,51 and 21 alleles identified at the HLA-A,B and C loci respectively,and the frequencies of these alleles were not significantly different between the PBC and normal control groups.However,the frequencies of A ＊11：01-B＊40：06 and A＊02：01-B＊l5：01 haplotypes were significantly higher in the PBC group than in the normal control group （7.53%vs.1.40%,P〈 0.01,OR =5.38; 6.85% vs.2.00%,P=0.003,OR =3.425）.Conclusion This study established the role of HLA class Ⅰ haplotypes in determining PBC susceptibility in a Chinese population.