中国汉族人群供-受者HLA-A、B、Cw、DRB1和DQB1高分辨等位基因频率分布及错配比例的研究  

A study on allele frequencies and mismatching proportion of HLA-A, B, Cw, DRBI and DQBI on high- resolution donor-recipient typing in Chinese Han population

作　　者：李杨[1] 何军[1] 鲍晓晶[1] 邱桥成[1] 袁晓妮[1] 徐超[1] 狄文英 张俭[2] 许学明[2] 陈子兴[1] 

机构地区：[1]苏州大学附属第一医院江苏省血液研究所 中国造血干细胞捐献者资料库HLA高分辨配型定点实验室,215006 [2]苏州市红十字中心血站

出　　处：《中华医学遗传学杂志》2011年第1期92-98,共7页Chinese Journal of Medical Genetics

基　　金：国家自然科学基金（81072435）;江苏省科技支撑项目（BE2010651）;江苏省六大人才高峰（07-B-21）;卫生部科研项目（LW201002）;苏州市基础设施项目（SZS201001）;苏州市中外国际合作项目（SWH0924）

摘　　要：目的从基因高分辨水平，分析中国汉族人群供-受者人类白细胞抗原（human leukocyte antigens，HLA）-A、B、Cw、DRB1、DQB1各位点等位基因频率和分布的多态性；及供-受者等位基因匹配情况。方法采用基因测序分型（sequence based typing，SBT）、序列特异性寡核苷酸探针法（sequence specific oligonucleotide probe，SSOP）和序列特异性引物法（sequence specific primer，SSP），对2540名中国汉族人的（其中1168名受者，1372名供者）DNA标本进行HLA高分辨基因分型，并作统计学处理。结果2540份样本中共检测到44种HLA-A等位基因，频率高于0．05的A＊1101、A＊2402、A＊0201、A＊0207、A＊3303、A＊0206、A＊3001共占80．4％；81种HLA-B等位基因，频率高于0．05的B＊4001、B＊4601、B＊5801、B＊1302、B＊5101共占43．0％；44种HLA-Cw等位基因，频率高于0．05的Cw＊0702、Cw＊0102、Cw＊0304、Cw＊0801、Cw＊0602、Cw＊0303、CW＊0302、Cw＊0401共占80．3％；61种HLA—DRBl等位基因，频率高于0．05的DRB1＊0901、DRB1＊1501、DRB1＊1202、DRB1＊0803、DRB1＊0701、DRB1＊0405、DRB1＊0301、DRB1＊1101共占70．1％；22种HLA-DQB1等位基因，频率高于0．05的DQB1＊0301、DQB1＊0303、DQB1＊0601、DQB1＊0602、DQB1＊0202、DQB1＊0302、DQB1＊0401、DQB1＊0502、DQB1＊0201共占87．4％。这5个位点均处于杂合子缺失状态，其中A、B、DRB1位点符合Hardy-Weinberg平衡（Hardy—Weinberg equilibrium，HWE）（P〉0．05）；Cw、DQB1位点偏离HWE（P〈0．05）；排除个别基因型观察值与期望值偏差较大外，这5个位点均符合HWE。在供一受者数据的比较中，HLA全相合（10／10）的比例仅22．4％；单个等位基因错配（9／10）的比例为24．6％；两个等位基因错配（8／10）的比例为26．3％。结论中国汉族人群高分辨水平HLA-A、B、Cw、DRB1、DQB1等位基因频率及分布特点，对非亲缘造血干细胞移植供者检索Objective To analyze the allele frequencies and polymorphism of human leukocyte antigens （HLA） -A, B, Cw, DRB1 and DQB1 between donors-recipients on high-resolution typing; and to analyze the matching and mismatching proportion between donors and recipients. Methods HLA high- resolution types were determined by sequence based typing （SBT）, sequence specific oligonucleotide probe （SSOP） and sequence specific primer （SSP） on 2540 unrelated Chinese Han individuals including 1168 recipients and 1372 donors, then statistical analyses were carried out. Results Forty-four HLA-A alleles were detected, and among them the frequencies of A ＊ 1101, A ＊ 2402, A ＊ 0201, A ＊ 0207, A ＊ 3303, A ＊0206 and A＊ 3001 exceeded 0.05, and accounted for 80.4%. Eightyone HLA-B alleles were detected, and frequencies of B＊ 4001, B＊ 4601, B＊ 5801, B＊ 1302 and B＊ 5101 exceeded 0. 05, and accounted for 43.0% of total. There were 44 HLA- Cw alleles, among them the frequencies of Cw ＊ 0702, Cw ＊ 0102, Cw ＊ 0304, Cw＊ 0801, Cw ＊ 0602, Cw ＊ 0303, Cw ＊ 0302 and Cw＊ 0401 exceeded 0.05, and were 80.3% of total. There were 61 HLA-DRB1 alleles, the frequencies of DRB1 ＊ 0901, DRB1 ＊ 1501, DRB1 ＊ 1202, DRB1 ＊ 0803, DRB1 ＊ 0701, DRB1 ＊ 0405, DRB1 ＊ 0301 and DRB1 ＊ 1101 exceeded 0. 05, and were 70. 1% of total. Finally, 22 HLA DQB1 alleles were detected, the frequencies of DQB1 ＊ 0301, DQB1 ＊ 0303, DQB1 ＊ 0601, DQB1 ＊ 0602, DQB1 ＊ 0202, DQB1 ＊ 0302, DQB1 ＊ 0401, DQB1 ＊ 0502 and DQB1 ＊ 0201 exceeded 0.05, and they were 87.4% of total. All the five loci were of heterozygote deficiency. The HLA-A, B and DRB1 loci conformed to Hardy-Weinberg equilibrium （HWE） （P2〉0. 05）; but HLA-Cw and HLA-DQB1 loci did not （P〈0.05）. Except several particular genotypes, all the five loci conformed to HWE. After comparing data between donors and recipients, only 22.4% of recipients found HLA matched donors （10/10） ：24. 6% of recipients found single HLA allele mismatc

关 键 词：人类白细胞抗原 高分辨基因分型 等位基因频率 多态性 造血干细胞移植 

分 类 号：R394[医药卫生—医学遗传学]