中国南方汉族造血干细胞捐献者HLA-A、-B、-C、-DRB1及-DQB1高分辨等位基因多态性分析  

Analysis on polymorphism of high-resolution HLA-A, -B, -C, -DRB1 and -DQB1 in hematopoietic stem cells donors of Chinese Han population from Southern China

作　　者：全湛柔 邓志辉[1] 周丹[1] 钟艳平[1] 陈浩 洪文旭[1] 邹红岩[1] Quan Zhanrou;Deng Zhihui;Zhou Dan;Zhong Yanping;Chen Hao;Hong Wenxu;Zou Hongyan(Institute of Transfusion Medicine of Shenzhen Blood Center,Shenzhen 518020,Guangdong Province,China)

机构地区：[1]广东省深圳市血液中心输血医学研究所,518020

出　　处：《国际输血及血液学杂志》2018年第6期497-505,共9页International Journal of Blood Transfusion and Hematology

基　　金：深圳市卫生计生委卫生计生系统科研项目(201506076);深圳市卫生计生委医疗卫生“三名工程”项目(SZSM201811092).

摘　　要：目的探讨中国南方汉族造血干细胞捐献者人类白细胞抗原(HLA)-A、-B、-C、-DRB1及-DQB1位点高分辨等位基因的多态性分布。方法选择2016年1月至2017年12月于中国造血干细胞捐献者资料库(CMDP)深圳分库登记的4 262例中国南方汉族造血干细胞捐献者为研究对象。采用PCR-序列特异性寡核苷酸探针(SSO)和二代测序(NGS)技术对本研究4 262例造血干细胞捐献者的HLA-A、-B、-C、-DRB1及-DQB1位点进行高分辨等位基因分型检测。采用直接计数法分别计算上述5个HLA位点的常见、确认及罕见等位基因频率。采用χ2检验判断研究对象的HLA-A、-B、-C、-DRB1及-DQB1各位点等位基因的分布是否符合Hardy-Weinberg平衡定律。结果①本研究4 262例中国南方汉族造血干细胞捐献者的HLA-A、-B、-C、-DRB1及-DQB1位点等位基因观察值与期望值分别比较,差异均无统计学意义(χ^2=295.068、572.482、355.205、362.584、312.150,P>0.05)。本研究4 262例造血干细胞捐献者的HLA-A、-B、-C、-DRB1及-DQBl位点基因型分布均符合Hardy-Weinberg平衡定律。②本研究4 262例中国南方汉族造血干细胞捐献者中,检出的HLA-A、-B、-C、-DRB1及-DQB1位点的等位基因分别为49、97、37、48和22种,其中等位基因频率>0.05的常见等位基因包括:HLA-A*11∶01、24∶02、02∶07、02∶01、33∶03和02∶03,累计等位基因频率为0.767 1;HLA-B*40∶01、46∶01、58∶01、13∶01和51∶01,累计等位基因频率为0.471 6;HLA-C*01∶02、07∶02、03∶04、08∶01、03∶02、06∶02和03∶03,累计等位基因频率为0.782 5;HLA-DRB1*09∶01、15∶01、12∶02、07∶01、08∶03、03∶01、11∶01和04∶05,累计等位基因频率为0.656 4;以及HLA-DQB1*03∶01、03∶03、06∶01、05∶02、03∶02、02∶01、05∶03、06∶02和02∶02,累计等位基因频率为0.877 6。③本研究4 262例中国南方汉族造血干细胞捐献者中,HLA-A、-B、-C、-DRB1及-DQB1位点的确认及罕见�Objective To explore the human leukocyte antigen (HLA)-A, -B, -C, -DRB1 and -DQB1 high-resolution alleles polymorphism in hematopoietic stem cells donors of Chinese Han population from Southern China.Methods A total of 4 262 cases hematopoietic stem cell donors of chinese Han population in Shenzhen China Marrow Donor Program (CMDP) from January 2016 to December 2017 were selected as subjects. HLA-A, -B, -C, -DRB1 and -DQB1 loci for high resolution typing of these 4 262 cases hematopoietic stem cell donors were detected by PCR-sequence-specific oligonucleotide probes (SSO) and next-generation sequencing (NGS) analysis. The frequencies of common, well-documented and rare alleles were studied by direct counting method. The χ^2 test was used to determine whether the distribution of HLA-A, -B, -C, -DRB1 and -DQB1 alleles of these 4 262 cases hematopoietic stem cell donors accorded with the Hardy-Weinberg equilibrium.Results ① Compared observed values of HLA-A, -B, -C, -DRB1 and -DQB1 alleles in these 4 262 cases hematopoietic stem cell donors of Chinese Han population from Southern China with the expected values, there were not statistically significance (χ^2=295.068, 572.482, 355.205, 362.584, 312.150; P>0.05), which indicated that the distribution of HLA-A, -B, -C, -DRB1 and -DQB1 alleles of all hematopoietic stem cell donors in this study conformed with Hardy-Weinberg equilibrium. ② The alleles of HLA-A, -B, -C, -DRB1 and -DQB1 loci in 4 262 cases hematopoietic stem cells donors of Chinese Han population from Southern China were 49, 97, 37, 48 and 22, respectively. Among them, the common alleles with frequencies higher than 0.05 included HLA-A*11∶01, 24∶02, 02∶07, 02∶01, 33∶03 and 02∶03; HLA-B*40∶01, 46∶01, 58∶01, 13∶01 and 51∶01; HLA-C*01∶02, 07∶02, 03∶04, 08∶01, 03∶02, 06∶02 and 03∶03; HLA-DRB1*09∶01, 15∶01, 12∶02, 07∶01, 08∶03, 03∶01, 11∶01 and 04∶05; and HLA-DQB1*03∶01, 03∶03, 06∶01, 05∶02, 03∶02, 02∶01, 05∶03, 06∶02 and 02∶02. For each

关 键 词：HLA抗原 等位基因 基因频率 聚合酶链反应 高分辨基因分型 常见等位基因 确认等位基因 罕见等位基因 聚合酶链反应-序列特异性寡核苷酸探针 二代测序 

分 类 号：R440[医药卫生—诊断学]