643例中国北方汉族急性淋巴细胞白血病患者人类白细胞抗原连锁不平衡分析  

Analysis of HLA haplotype frequency and linkage disequilibrium in patients with acute lymphoblastic leukemia from Northern Chinese Han~

作　　者：高素青[1] 程良红[1] 卢亮[1] 金士正[1] 程曦[1] 张印则[1] 邹红岩[1] 邓志辉[1] 

机构地区：[1]广东省深圳市血液中心研究所,中华骨髓库深圳HLA分型实验室,518035

出　　处：《中华医学遗传学杂志》2009年第1期82-86,共5页Chinese Journal of Medical Genetics

基　　金：深圳市科技计划项目（200603202）;中华骨髓库合作项目;志谢 感谢中国造血干细胞捐献者资料库管理中心领导、专家和同仁对本项目的支持和帮助.感谢深圳市第二人民医院血液病研究所汪明春教授和李明主任的指导,感谢深圳大学超级计算中心、数学系李国教授、李飞鹏老师在编写计算机程序上和数学统计学方面的帮助

摘　　要：目的分析643例中国北方汉族急性淋巴细胞白血病（acute lymphoblastic leukemia，ALL）患者组和20359名健康对照组的人类白细胞抗原（human leukocyte antigen，HLA）HLA—AB、BDR和A—B-DR单倍型频率及连锁不平衡分布差异。方法应用最大似然性算法（expectation—maximization，EM）计算患者组和对照组的HLA-A-B、B—DRB1和A—B—DRB1单倍型频率及连锁不平衡参数，采用x^2检验比较其分布差异。结果HLA-A30-B13、A2-B46、A33-B58，B13-DR7、B46-DR9、B52-DR15、B58-DR17，A30-B13DR7、A33-B58-DR17和A1-B37-DR10单倍型是两组常见、共有呈强连锁不平衡单倍型。A30—B13、A2-B46、A33-B44、B13-DR7、A30-B13-DR7和A2-B46-DR9的单倍型频率和连锁不平衡水平，患者组低于对照组，差异有统计学意义（x^2〉3．84，P〈0．05）。A2-B52、A2-B27、A24-B8，B60-DR9、B27-DR4、B52-DR14、B44-DR17、B27-DR12、和A11-B27-DR12的单倍型频率和连锁不平衡水平，患者组高于对照组，差异有统计学意义（x^2〉3．84，P〈0．05）。结论643例北方汉族ALL患者组HLA-A-B、B-DRB1、A—B-DRB1单倍型频率分布及连锁不平衡遗传特征和对照组具有高度的同源性。患者组与对照组之间的部分HLA单倍型频率及连锁不平衡分布存在统计学差异。本研究结果为ALL与HLA疾病相关性及HLA相合供者的寻找提供了基础数据。Objective To analyze the difference between the frequencies of HLA A-B, B-DRB1 and A-B-DRB1 haplotype, as well as their linkage disequilibrium pattern in patients with acute lymphoblastic leukemia（ALL） and healthy controls from Northern Chinese Han. Methods The frequencies of HLA-A- B, B-DRB1, A-BDR haplotypes and linkage disequilibrium were estimated by Expectation Maximization method based on the genotypes of 643 patients with ALL and 2 0359 unrelated healthy donors, and the statistical significance between the two groups were estimated by chi-square test. Linkage disequilibrium was analyzed with population genetic methods. Results The most common HLA-A-B, BDRB1, and A-B- DR haplotypes were A30-B13, A2 B46, A33-B58, B13-DRT, B46-DR9, B52 DR15, B58-DR17, A30-B13 DR7, A33-B58-DR17 and A1-B37-DR10 in both groups. The frequencies of A30-B13, A2 B46, A33-B44, B13 DR7, A30-B13-DR7 and A2 B46 DR9 haplotypes and linkage disequilibrium value were significantly decreased （P〈0. 05） in the patient group than that in the control group. On the other hand, the frequencies of A2-B52, A31 B61, A24-BS, B60-DR9, B27 DR4, B52-DR14, B44 DR17, B27-DR12 and All-B27-DR12 haplotypes and linkage disequilibrium value were significantly increased （P〈0.05） in the patient group than that in the control group. Conclusion There are some common and positive linkage disequilibrium haplotypes in both the ALL patients and the healthy donors in Northern Chinese Han. Interestingly, some haplotypes and their linkage disequilibrium patterns had significantly different distributions between the two groups. The study provided basic data for the relationship of ALI. and HLA haplotype and for finding the HLA-A, B, DR matching donors.

关 键 词：急性白血病 人类白细胞抗原 单倍型 连锁不平衡 

分 类 号：R686[医药卫生—骨科学]