39628份造血干细胞捐献者HLA分型数据分析

HLA typing data from 39628 hematopoietic stem cell donors:A retrospective study

目的:了解重庆地区干细胞捐献者HLA-A,-B,-C,-DRB1及DQB1位点基因多态性分布特征,探讨人类白细胞抗原(HLA)单倍体特征的临床意义。方法:回顾性收集2002—2019年重庆地区上传中华骨髓库干细胞捐献者HLA分型数据39628份,使用直接计数法计算等位基因频率,利用Arlequin 3.5软件进行Hardy-Weinberg平衡检验及估算单倍型频率。结果:39628份HLA分型数据包括高分数据12085份、G组数据5751份、中低分数据21792份。将基因型转化为对应的抗原特异性后,共检出HLA-A位点抗原特异性19个、HLA-B位点抗原特异性37个、HLA-C位点抗原特异性13个、HLA-DRB1位点抗原特异性15个,HLA-DQB1位点抗原特异性5个。其中,频率最高的抗原分别为HLA-A*02(30.23%)、B*40(17.29%)、C*03(23.02%)、DRB1*09(17.09%)、DQB1*03(44.97%)。12085份高分数据中观察到HLA-A-B-DR单体型3738种,频率大于0.01的共9种。三位点单倍型中A*02:07-B*46:01-DRB1*09:01(5.34%)频率最占优势,A*33:03-B*58:01-DRB1*03:01(2.43%)次之,与大连等北方地区比较差异有统计学意义(P<0.05)。理论上在重庆骨髓库中寻找到至少1例HLA-ABDR抗原全配合供者的概率为47.95%。结论:重庆地区汉族人群HLA等位基因分布具有自身特征,目前重庆地区干细胞捐献者资料库的库容量需进一步扩充。

Objective:To understand the characteristics of HLA-A,-B,-C,-DRB1 and DQB1 gene polymorphisms of stem cell donors,and explore the clinical significance of HLA haploid characteristics.Methods:A total of 39628 HLA typing data of stem cell donors from CMDP were collected retrospectively.Allele frequencies were calculated by direct counting method.Arlequin3.1 software was used to perform Hardy-Weinberg balance test and estimate haplotype frequency.Results:The 39628 HLA typing data included 12085 high resolution data,5751 G-group data,and 21792 middle-low resolution data.After genotypes were transformed into corresponding antigen specificity,19 HLA-A locus phenotype specificities were identified,37 HLA-B locus phenotype specificities were identified,13 HLA-C locus phenotype specificities were identified,15 HLA-DRB1 locus phenotype specificities were identified,5 HLA-DQB1 locus phenotype specificities were identified.The highest frequency antigens were HLA-A*02(30.23%),B*40(17.29%),C*03(23.02%),DRB1*09(17.09%)and DQB1*03(44.97%).In 12085 high-resolution data,3738 haplotypes of HLA-A-B-DR were observed,of which 9 frequencies were greater than 0.01,the highest frequencies haplotypes were A*02:07-B*46:01-DRB1*09:01(5.34%),followed by A*33:03-B*58:01-DRB1*03:01(2.43%).It was significantly different from Dalian and other northern regions(P<0.05).In theory,the probability of finding at least one HLA-ABDR matched donor in Chongqing marrow bank was 47.95%.Conclusion:The distribution of HLA alleles in Chongqing had its own characteristics.The stem cell donor database should be further expanded.