Wu Qiang-Ju, Liu Meng-Li, Qi Jun, Liu Sheng, Zhang Yan, Wei Xiao-Qian
Blood Center of Shanxi Province, Xi'an 710061, China.
Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2007 Apr;15(2):357-63.
The study was aimed to investigate the human leukocyte antigen (HLA)-A, B, DRB1 alleles and haplotype frequencies and the characteristics of linkage disequilibrium in north Chinese Han bone marrow donors. HLA phenotype data of 11 755 north Chinese Han bone marrow donors were identified by PCR-SSP and PCR-SSO. HLA-A, B, DRB1 allele and haplotype frequencies were calculated by computer software named Arleguin which was based on Expectation-Maximization (EM) algorithms. The results showed that the population of 11755 unrelated-donors was tested by Hardy-Weinberg equilibrium, and 18,42 and 15 specificities of HLA alleles were identified on the HLA-A, B, DRB1 locus respectively, including HLA-A25, B42, B53, B73 and DR3 which were rarely reported in Han population. HLA-A36, A43, A80, B78, B82 and DR18 were not detected in this study. The most frequent alleles with a frequency of over 0.05 were HLA-A02, A11, A24, A33, A30, A01, A03, A13, B62, B51, B46, B60, B61, B35, B44, DRB115, DRB109, DRB104, DRB107, DRB112, DRB111, DRB114, DRB108, DRB1*13. There were a total of 2 026 kinds of HLA-A-B-DR haplotypes (with a frequency of over 10(-6)) to be obtained. The each frequency of 26 kinds of three-locus haplotypes including HLA-A30-B13-DR7, A2-B46-DR9, A33-B58-DR17 etc was higher than 0.005. A30-B13-DR7 was the most frequent haplotype in north Chinese Han population. There were a total of 538 kinds of haplotypes for HLA-A-B, 227 kinds for A-DR and 522 kinds for B-DR to be obtained, and there were 409, 195, 423 kinds of haplotypes respectively with a frequency higher than 10 - 6. There were 28 kinds of HLA-A-B haplotypes including A30-B13, A2-B46, A33-B58 etc, 26 kinds of HLA-A-DR haplotypes including A2-DR9, A2-DR15, A30-DR7 etc, and 24 kinds of HLA-B-DR haplotypes including B13-DR7, B46-DR9, B13-DR12 etc with a frequency higher than 0.01. 296 (72%) kinds of HLA-A-B, 130 (67%) kinds of A-DR and 308 (73%) kinds of B-DR haplotypes were statistical linkage disequilibrium. HLA-A30-B13, A33-B58, A1-B37, A30-DR7, A33-DR13, A1-DR10, B37-DR10, B8-DR17, B13-DR7, B58-DR17 were significant positive linkage disequilibrium. It is concluded that this HLA-A, B, DRB1 gene and haplotype frequencies and linkage disequilibrium data with the largest sample size up to now is unique in north Chinese Han population. The study will be helpful to find matched donors for patients and establish the important foundation for further studying of transplantation immunity, HLA-related diseases and population genetics of this area.
本研究旨在调查中国北方汉族骨髓供者的人类白细胞抗原（HLA）-A、B、DRB1等位基因及单倍型频率，以及连锁不平衡特征。采用聚合酶链反应-序列特异性引物（PCR-SSP）和聚合酶链反应-序列特异性寡核苷酸探针（PCR-SSO）方法对11755名中国北方汉族骨髓供者的HLA表型数据进行检测。运用基于期望最大化（EM）算法的Arleguin计算机软件计算HLA-A、B、DRB1等位基因及单倍型频率。结果显示，对11755名无关供者群体进行Hardy-Weinberg平衡检验，在HLA-A、B、DRB1基因座上分别鉴定出18、42和15个HLA等位基因特异性，其中包括HLA-A25、B42、B53、B73和DR3，这些在中国汉族人群中鲜有报道。本研究未检测到HLA-A36、A43、A80、B78、B82和DR18。频率超过0.05的最常见等位基因有HLA-A02、A11、A24、A33、A30、A01、A03、A13、B62、B51、B46、B60、B61、B35、B44、DRB115、DRB109、DRB104、DRB107、DRB112、DRB111、DRB114、DRB108、DRB1*13。共获得2026种HLA-A-B-DR单倍型（频率超过10^(-6)）。包括HLA-A30-B13-DR7、A2-B46-DR9、A33-B58-DR17等在内的26种三位点单倍型的频率均高于0.005。A30-B13-DR7是中国北方汉族人群中最常见的单倍型。共获得538种HLA-A-B单倍型、227种A-DR单倍型和522种B-DR单倍型，频率高于10^(-6)的分别有409种、195种和423种。频率高于0.01的HLA-A-B单倍型有28种，包括A30-B13、A2-B46、A33-B58等；HLA-A-DR单倍型有26种，包括A2-DR9、A2-DR15、A30-DR7等；HLA-B-DR单倍型有24种，包括B13-DR7、B46-DR9、B13-DR12等。296种（72%）HLA-A-B单倍型、130种（67%）A-DR单倍型和308种（73%）B-DR单倍型存在统计学连锁不平衡。HLA-A30-B13、A33-B58、A1-B37、A30-DR7、A33-DR13、A1-DR10、B37-DR10、B8-DR17、B13-DR7、B58-DR17存在显著正连锁不平衡。结论：本研究是目前样本量最大的关于中国北方汉族人群HLA-A、B、DRB1基因及单倍型频率和连锁不平衡的数据，具有独特性。该研究有助于为患者寻找匹配供者，并为进一步研究该地区的移植免疫、HLA相关疾病及群体遗传学奠定重要基础。
