山东滨州地区汉族造血干细胞捐献志愿者HLA-A、-B、-DRB1高分辨等位基因及其单体型多态性分析  

Distribution characteristics of high-resolution alleles and haplotypes of HLA-A,-B and-DRB1 in Han Nationality hematopoietic stem cell voluntary donors in Binzhou of Shandong Province

作　　者：孙春莲 李洪波 邵静茹 Sun Chunlian;Li Hongbo;Shao Jingru(Binzhou Central Blood Station,Binzhou 256600,Shandong Province,China;Shandong Blood Center,Jinan 250014,Shandong Province,China)

机构地区：[1]山东省滨州市中心血站,256600 [2]山东省血液中心,济南250014

出　　处：《国际输血及血液学杂志》2021年第2期168-177,共10页International Journal of Blood Transfusion and Hematology

摘　　要：目的探讨山东滨州地区汉族造血干细胞(HSC)捐献志愿者中人类白细胞抗原(HLA)-A、-B、-DRB1高分辨等位基因及其单体型的多态性分布特征。方法选择2010年1月至2018年12月,于滨州市中心血站行HLA-A、-B、-DRB1高分辨基因分型的2620例无亲缘关系健康汉族HSC捐献志愿者为研究对象。HSC捐献志愿者年龄为18~45岁;男性志愿者为1482例,女性为1138例。采用PCR-序列特异的寡核苷酸探针杂交(SSOP)法,对HSC捐献志愿者全血基因组DNA标本的HLA-A、-B、-DRB1位点进行高分辨基因分型。采用直接计数法计算HSC捐献者HLA-A、-B、-DRB1的基因频率和基因型频率。采用Arlerquin 3.5统计学软件计算HLA-A、-B、-DRB1等位基因单倍型频率,并对HLA-A、-B、-DRB1的基因分布进行Hardy-Weinberg平衡检验。滨州地区汉族HSC捐献志愿者与文献报道的中国其他地区汉族人群的HLA-A、-B、-DRB1等位基因频率比较,采用χ^(2)检验。本研究遵循的程序符合2013年修订版《世界医学协会赫尔辛基宣言》要求,并且与所有受试者签署《中国造血干细胞捐献者资料库志愿捐献者同意书》。结果①本组2620例HSC志愿捐献者的HLA-A、-B、-DRB1基因分布的Hardy-Weinberg平衡检验结果显示,各基因位点基因频率的观察值与期望值分别比较,差异均无统计学意义(P>0.05),即本组HSC捐献志愿者HLA-A、-B、-DRB1基因分布,符合Hardy-Weinberg平衡定律。②本组2620例HSC捐献者DNA标本中,检出的HLA-A、-B、-DRB1等位基因分别为52、89和52种,多态性最高基因组分别为A*02组(11种),B*15组(20种)和DRB1*14组(11种)。2620例志愿者的血样DNA标本中,检出HLA-A-B-DRB1单倍型为2604种,其中频率>0.10%的单倍型为133种,频率>1.00%的单倍型为A*30:01-B*13:02-DRB1*07:01(1.77%)和A*02:01-B*13:02-DRB1*07:01(1.13%)。③本组2620例志愿者的血样DNA标本中,检出等位基因频率>1.00%的HLA-A、-B、-DRB1等位基因共计65个,并且在文�Objective To explore distribution characteristics of high-resolution alleles and haplotypes of HLA-A,-B and-DRB1 in Han Nationality hematopoietic stem cell(HSC)voluntary donors in Binzhou of Shandong Province.Methods From January 2010 to December 2018,a total of 2620 unrelated healthy Han Nationality HSC voluntary donors who underwent HLA-A,-B,-DRB1 high-resolution genotyping in Binzhou Central Blood Station were selected as research subjects.The age of HSC voluntary donors was 18 to 45 years old.And there were 1482 male and 1138 female HSC donors.The PCR-sequence specific oligo-nucleotide probe(SSOP)method was used to perform high-resolution genotyping on HLA-A,-B and-DRB1 loci of whole blood genomic DNA samples of HSC donors.The direct counting method was used to calculate gene frequency and genotype frequency of HLA-A,-B and-DRB1 of HSC donors.Arlerquin 3.5 statistical software was used to calculate haplotype frequencies of HLA-A,-B and-DRB1 alleles,and the Hardy-Weinberg equilibrium test was performed on gene distribution of HLA-A,-B and-DRB1.HLA-A,-B and-DRB1 allele frequencies between Han Nationality HSC donors in Binzhou area and Han Nationality populations in other regions of China reported in literatures,were compared by Chi-square test.The procedure followed in this study complied with the requirements of the 2013 revised World Medical Association Declaration of Helsinki,and all subjects signed the Chinese Hematopoietic Stem Cell Donor Database Volunteer Donor Consent.Results①The Hardy-Weinberg balance test results showed that there were no statistical differences between observed and expected value of HLA-A,-B and-DRB1 gene frequencies of 2620 HSC donors in this study(P>0.05),which indicated that distribution of HLA-A,-B and-DRB1 genes of HSC donors in this study complied with the Hardy-Weinberg equilibrium law.②In 2620 DNA samples from HSC donors in this study,there were 52,89 and 52 alleles in HLA-A,-B and-DRB1 locus,respectively.The groups with the highest polymorphism at each locus were A*02 gr

关 键 词：HLA抗原 等位基因 基因频率 单元型 高分辨基因分型 

分 类 号：R457.7[医药卫生—治疗学]