HLA-DRB1,-DQB1,-DPB1等位基因及单体型多态性与北方汉族急性髓系白血病(非M3型)的关联性研究  

Association of HLA-DRB1,-DQB1,-DPB1 alleles and haplotype polymorphisms with acute myeloid leukemia (non-M) in northern Han population

作　　者：齐珺[1] 王天菊[1] 陈乐 王满妮[1] 王小芳[1] 杜丹 尚利侠 武君华[1] 房婕[1] 李恒新 QI Jun;WANG Tianju;CHEN Le;WANG Manni;WANG Xiaofang;DU Dan;SHANG Lixia;WU Junhua;FANF Jie;LI Hengxin(High-resolution HLA Typing Ixiboratory of the Chinese Marrow Donor Program,Shanxi Blood Center Institute of Xi'an Blood Bank,Xi'an 710061,China;Management Center for the Data Bank of Chinese Hematopoietic Stem Cell Donor)

机构地区：[1]陕西省血液中心西安市中心血站中华骨髓库HLA高分辨分型确认实验室,陕西西安710061 [2]中国造血干细胞捐献者资料库管理中心

出　　处：《中国输血杂志》2021年第2期101-106,共6页Chinese Journal of Blood Transfusion

基　　金：中国输血协会威高科研基金(CSBT-WG-2017-06);西安市卫生健康委员会科研项目Ⅰ类(J201701003)。

摘　　要：目的探讨HLAⅡ类(-DRB1,-DQB1,-DPB1)等位基因及单体型多态性与北方汉族急性髓系白血病(acute myeloid leukemia, AML)的易感相关性。方法以824名正常非亲缘造血干细胞捐献者(2016年1月—2019年9月)为对照,应用聚合酶链反应-测序分型(PCR-SBT)、下一代测序(NGS-ION S5TM)技术、基于LABScan? 3D平台的聚合酶链反应-序列特异寡核苷酸探针技术(PCR-SSO)等方法对308例AML(非M3型)患者进行HLAⅡ类(-DRB1,-DQB1,-DPB1)基因高分辨分型,用Arlequin 3.5.2.2软件计算HLA基因频率和单体型频率,计算疾病优势比(odds ratio,OR)进行病例对照研究。结果经χ^(2)检验、连续校正显示非M3型AML患者的HLA-DRB1*07∶01(14.61%vs 9.53%,P<0.01)、HLA-DQB1*02∶02(12.82%vs 8.31%,P<0.01)、HLA-DQB1*06∶02(11.53%vs 8.74%,P<0.05)和HLA-DPB1*17∶01(5.84%vs 3.16%,P<0.01)基因频率显著高于对照组,经Bonferroni校正后HLA-DRB1*07∶01(Pc<0.05)、HLA-DQB1*02∶02(Pc<0.05)和HLA-DPB1*17∶01(Pc<0.05)频率仍高于对照组,与AML呈强相关,OR分别为1.62(95%CI=1.23~2.14)、1.62(95%CI=1.21~2.18)和1.91(95%CI=1.23~2.94);AML患者的2座位单体型HLA-DRB1*07∶01-DQB1*02∶02频率经Bonferroni校正后仍高于对照组(12.66%vs 8.19%,Pc<0.05);3座位单体型HLA-DRB1*07∶01-DQB1*02∶02-DPB1*17∶01频率高于对照组,与AML呈强相关,是AML的易感单体型。结论本研究首次获得HLAⅡ(-DRB1,-DQB1,-DPB1)基因及单体型多态性与北方汉族AML相关性的资料,HLA-DRB1*07∶01、HLA-DQB1*02∶02、HLA-DPB1*17∶01及单体型HLA-DRB1*07∶01-DQB1*02∶02-DPB1*17∶01是北方汉族发生AML的风险基因及易感单体型,基于HLA单体型的风险预测可能比基于单个等位基因的风险计算更为精确。Objective To explore the association of HLAII(-DRB1,-DQB1,-DPB1) alleles and haplotypes polymorphisms with acute myeloid leukemia(AML) in northern Han population.Methods A total of 308 AML(non-M3) patients(patient group) and 824 unrelated healthy bone marrow donors(control group) were genotyped at a high-resolution level using polymerase chain reaction-sequence-based typing(PCR-SBT), next-generation sequencing(NGS) with Ion Torrent S5 platform and sequence specific oligonueleotide probes(SSO) with LABScan■ 3 D platform. Frequencies of HLA II alleles and haplotypes were calculated with Arlequin 3.5.2.2 software. The odds ratio(OR) of AML was also calculated for case-control study. Results By χ^(2) test and correction, an increased frequency of HLA-DRB1*07∶01(14.61% vs 9.53%, P<0.01), HLA-DQB1*02∶02(12.82% vs 8.31%, P<0.01), HLA-DQB1*06∶02(11.53% vs 8.74%, P<0.05) and HLA-DPB1*17∶01(5.84% vs 3.16%, P<0.01) among AML patients was discovered in significant comparison with the control group. After Bonferroni correction, the frequency of HLA-DRB1*07∶01(Pc<0.05), HLA-DQB1*02:02(Pc<0.05) and HLA-DPB1*17∶01(Pc<0.05) in AML patients were still higher than those in the control group, which had a strong positive correlation with AML(OR=1.62(95% CI=1.23~2.14)), 1.62(95% CI=1.21~2.18) and 1.91(95% CI=1.23~2.94),respectively. The frequency of two loci haplotype HLA-DRB1*07∶01-DQB1*02∶02 in AML patients was still higher than that of the control group after Bonferroni correction(12.66% vs 8.19%, Pc<0.05). The frequency of the 3 loci haplotype HLA-DRB1*07∶01-DQB1*02∶02-DPB1*17∶01, as a susceptible haplotype of AML, was higher than that of the control group and was strongly correlated with AML.Conclusion The data on the association of HLA II(-DRB1,-DQB1,-DPB1) alleles and haplotype polymorphisms with AML in northern Han populations was obtained in this study. HLA-DRB1*07∶01, HLA-DQB1*02∶02, HLA-DPB1*17∶01 and the HLA-DRB1*07∶01-DQB1*02∶02-DPB1*17∶01 haplotype are the risk genes and susceptible e

关 键 词：急性髓系白血病 人类白细胞抗原 HLAⅡ类 单体型 基因频率 

分 类 号：R457.1[医药卫生—治疗学] R733.71[医药卫生—临床医学]