肝硬化患者人类白细胞抗原-DRB1和DPBl基因多态性的临床意义  

Clinical significance of HLA-DRB1 and HLA-DPB1 gene polymorphisms in cirrhosis patients

作　　者：赵巍烽 刘淑媛[1] 杜敬佩[1] 李长安[1] 窦芊 尚佳[2] 

机构地区：[1]新乡医学院第三附属医院感染科,新乡453003 [2]河南省人民医院感染科

出　　处：《中华肝脏病杂志》2014年第10期744-746,共3页Chinese Journal of Hepatology

基　　金：河南省医学科技攻关项目（201003107）

摘　　要：目的探讨人类白细胞抗原（HLA）-DRBl和DPBl基因多态性与肝硬化易感性的关联。方法收集肝硬化患者168例作为研究组，其生物学父母作为对照组。运用聚合酶链反应扩增及单核苷酸多态性的分子生物学技术，检测HLA-DRBl和DPBl基因rs24755213、rs202176660基因多态性，进行肝硬化与HLA-DRBl和DPBl基因多态性的关联分析和单体型相对风险率分析。哈迪温伯格吻合度检验进行群体分析，P〈0.05为差异有统计学意义。结果HLA-DRB1单核昔酸多态性基因（SNP）位点rs24755213为A／G两种基因型，HLA-DPBl基因SNP位点rs202176660为C／T两种基因型，Hardy-Weinberg平衡检验结果表明吻合度良好；HLA-DRBl和DPBl基因SNP位点rs24755213与肝硬化相关联（P=0.014），其中等位基因A为危险因素（Z=2.33），G是保护因素（Z=-2.33）；rs202176660等位基因多态性与肝硬化相关联（P=0.026），其中等位基因C是保护因素（z=-2.06），T为危险因素（Z=2.06）。rs24755213、-rs202176660单体型的G／T、A／C与肝硬化相关联（Z值分别为-2.12、2.09，P值分别为0.037、0.002）。结论HLA-DRBl和DPBl基因的单核苷酸表型差异与肝硬化的发生和发展关系密切。Objective To investigate the genetic association between cirrhosis and polymorphisms in the genes encoding major histocompatibility complex, class Ⅱ（HLA）- DR beta 1 （DRB1） and HLA- DP beta 1 （DPB1）. Methods A population of 168 parent/offspring trios, in which the proband had a diagnosis of hepatitis B virus infection with clinical signs of cirrhosis. The HLA-DRB1 and DPB 1 gene polymorphisms of rs24755213 and rs202176660 were detected by PCR and single nucleotide polymorphism （SNP） genotyping. Correlation analysis and haplotype relative risk analysis were carried out. Results A/G genotypes were detected in rs24755213 of HLA-DRB1 and C/T genotypes were detected in rs202176660 of DPB1. The rs24755213 allele was associated with cirrhosis （P = 0.014）, with the G allele identified as a protective factor （Z = -2.33） and the A allele identified as a hazard factor （Z= 2.33）. The rs202176660 allele was also associated with cirrhosis （P = 0.026）, with the T allele identified as a protective factor （Z = -2.06） and the C allele identified as a hazard factor （Z = 2.06）. The haplotypes of G/T and A/C in rs24755213 and rs202176660 respectively were associated with cirrhosis （P = 0.037 and 0,002, Z = -2.12 and 2.09 respectively）. Conclusion In this group of Chinese patients with hepatitis B virus-related cirrhosis, polymorphisms in the HLA-DRB1 and DPB1 genes were associated with cirrhosis.

关 键 词：肝硬化 多态性 单核昔酸 人类白细胞抗原 

分 类 号：R725.6[医药卫生—儿科]