65例北方汉族患者HLA基因多态性与再生障碍性贫血的相关性研究  

Relationship between HLA Gene Polymorphism and Aplastic Anemia in Northern Chinese Han Patients

作　　者：王博婧 吴亚妹[1] 李晓红[1] 徐丽昕[1] 王静[1] 闫蓓[1] 汪海涛[1] 李松威[1] 高亚会 张甜甜[1] 王丽[1] 张雅茜[1] 吴晓雄[1] WANG Bo-Jing;WU Ya-Mei;LI Xiao-Hong;XU Li-Xin;WANG Jing;YAN Bei;WANG Hai-Tao;LI Song-Wei;GAO Ya-Hui;ZHANG Tian-Tian;WANG Li;ZHANG Ya-Qian;WU Xiao-Xiong(Department of Hematology,First Affiliated Hospital,Chinese PLA General Hospital,Beijing 100048,China)

机构地区：[1]解放军总医院第一附属医院血液科,北京100048

出　　处：《中国实验血液学杂志》2018年第6期1731-1737,共7页Journal of Experimental Hematology

基　　金：国家自然科学基金青年科学基金项目(81700122);首都临床特色应用研究与成果推广项目(Z171100001017156);解放军总医院科技创新苗圃基金项目(17KMM29)

摘　　要：目的:探讨65例北方汉族患者HLA-A、-B、-C、-DRB1、-DQB1基因多态性与再生障碍性贫血(aplastic anemia, AA)的相关性。方法:采用聚合酶链式反应联合序列特异性寡核苷酸探针(polymerase chain reaction-sequence specific oligonucleotide, PCR-SSO)为基础的分型技术,对65例AA患者样本及772例正常对照样本的HLA-A、-B、-C、-DRB1、-DQB1基因位点进行高分辨分型,通过χ2检验、连续校正χ2检验、双侧Fisher精确概率法和优势比(odds ratio, OR)分析HLA-A、-B、-C、-DRB1、-DQB1基因与AA的相关性。结果:AA病例组与正常对照组相比,HLA-B*1302(10%vs 4.21%)、HLA-B*3501(7.69%vs 3.89%)、HLA-DRB1*0701(10%vs 4.73%)、HLA-DRB1*0901(19.23%vs 7.58%)、HLA-DQB1*0202(9.23%vs 3.76%)基因频率显著升高(P<0.05);卡方值分别为9.049、4.336、6.838、20.974、8.968,OR比分别为2.528、2.061、2.239、2.904、2.605,而HLA-A*3303(1.54%vs 6.93%)、HLA-DQB1*0302(1.54%vs 6.02%)基因频率显著减低(P<0.05)。卡方值分别为5.726、4.505,OR比分别为0.210、0.244。结论:65例北方汉族患者中HLA-A、-B、-DRB1、-DQB1基因多态性与再生障碍性贫血发生相关,HLA-B*1302、HLA-B*3501、HLA-DRB1*0701、HLA-DRB1*0901、HLA-DQB1*0202可能为AA发生的易感基因,HLA-A*3303、HLA-DQB1*0302可能为AA的保护性基因。Objective: To explore the relationship between HLA-A, -B, -C, -DRB1, -DQB1 gene polymorphism and aplastic anemia (AA)of 65 cases in Northern China.Methods: The high resolution genotyping of HLA-A, -B, -C,-DRB1, -DQB1 alleles in 65 AA patients and 772 healthy controls was performed with polymerase chain reactionsequence specific oligonucleotide (PCR-SSO), the relationship between HLA-A, -B, -C, -DRB1, -DQB1 gene polymorphism and aplastic anemia was analyzed by Pearson Chi-square,Continuity Correction, Two-sided Fisher ′s Exact Test and Odds Ratio.Results: The HLA-B*1302(10% vs 4.21%), B*3501(7.69% vs 3.89%), DRB1* 0701(10% vs 4.73%), DRB1*0901(19.23% vs 7.58%), DQB1*0202(9.23% vs 3.76%) gene frequency in AA patients was higher than those in health controls, the difference was statistically significant (P<0.05), the χ^2 were 9.049, 4.336, 6.838,20.974 and 8.968, OR ratio was 2.528, 2.061, 2.239, 2.904 and 2.605.However, the HLA-A*3303(1.54% vs 6.93%),DQB1*0302(1.54% vs 6.02%) gene frequency in AA patients was lower than those in healthy controls, the difference was statistically significant (P<0.05), the χ^2 was 5.726 and 4.505, the OR ratio were 0.210 and 0.244.Conclusion:The polymorphism of HLA-A, -B, -DRB1, -DQB1 alleles is associate with AA in these patient cases, the HLA-B*1302,HLA-B*3501, HLA-DRB1*0701, HLA-DRB1*0901 and HLA-DQB1*0202 may be sensitive genes to AA, while the HLA-A*3303 and HLA-DQB1*0302 may be protective genes on AA.

关 键 词：再生障碍性贫血 人类白细胞抗原 HLA基因多态性 

分 类 号：R556.5[医药卫生—血液循环系统疾病]