HLA-A/B/C/DRB1/DQB1基因多态性与急性淋巴细胞白血病关联分析  

Relationship between genetic polymorphism of human leukocyte antigen HLA-A/B/C/DRB1/DQB1 and acute lymphoblastic leukemia

作　　者：刘楠[1] 林晓娥[1] 袁方[1] 梁飞[1] 代东发[1] 孙玉英[1] 奚永志[1] 

机构地区：[1]军事医学科学院附属医院免疫学实验室,国家生物医学分析中心免疫学实验室,北京100071

出　　处：《军事医学》2013年第8期574-577,共4页Military Medical Sciences

基　　金：国家"973"重大基础研究基金资助项目(2009CB515509);国家自然科学基金资助项目(30470751)

摘　　要：目的探讨人类白细胞抗原(HLA)-A/B/C/DRB1/DQB1基因多态性与急性淋巴细胞白血病(acute lymphoblastic leukemia,ALL)的关联性。方法采用聚合酶链反应序列特异性引物(PCR-SSP)分型技术对277例ALL患者以及1370例健康无血缘关系对照组进行HLA-A/B/C/DRB1/DQB1基因分型,并将结果采用病例对照研究方法进行基因频率、单倍型频率以及疾病发生相对危险率(RR)的研究。结果 ALL患者Cw7的基因频率较对照组升高(P<0.05),其RR为6.0202;而HLA-A30、B13及Cw4基因频率较对照组降低(P<0.05);其RR分别为0.5181、0.6907和0.4769。两位点单倍型B13-Cw6在疾病组较对照组频率显著性升高(P<0.05),其RR为4.7861。两位点单倍型A30-B13、A30-DR7、B13-DR7以及扩展单倍型A30-B13-Cw6-DR7-DQ2在疾病组均较对照组频率显著性降低(P<0.05),其RR分别为0.3566、0.4933、0.4824和0.4052。结论我们在中国汉族人群中通过大样本量的病例对照研究来探寻HLA基因多态性与ALL之间的关联性,并取得了初步结果。HLA-Cw7与ALL的易感性相关;HLA-A30、B13、Cw4基因频率则与ALL发生呈负相关,可能是ALL的保护性基因;某些HLA单倍型亦与ALL的发生有关。Objective To study the relationship between genetic polymorphism of human leukocyte antigen（HLA） and acute lymphoblastic leukemia（ALL）.Methods Two-hundred and seventy-seven ALL patients and 1370 healthy unrelated control group were genotyped using polymerase chain reaction sequence-specific primers（PCR-SSP） typing method for HLA-A / B / C / DRB1 / DQB1 loci.The results of the two groups were analyzed by case control study to discover the different distribution in gene,haplotype and extended haplotype levels and to investigate the relative risk（RR） of ALL.Results The gene frequencies of Cw7 in ALL group were significantly higher（P〈0.05） than in control group,and the RR was 6.0202.However,HLA-A30,B13 and Cw4 frequencies were significantly lower（P〈0.05） in ALL group,and their RR was 0.5181,0.6907 and 0.4769,respectively.The haplotype frequencies of B13-Cw6 were significantly higher（P〈0.05） in ALL group,and the RR was 4.7861.The frequencies of A30-B13-Cw6-DR7-DQ2,A30-B13,A30-DR7 and B13DR7 were significantly lower（P〈0.05） in ALL group,and their RR was 0.4052,0.3566,0.4933 and 0.4824,respectively.Conclusion The relationship between HLA genetic polymorphism and ALL in large scale case-control studies is found to some extent.HLA-Cw7 is the susceptibility genes for ALL while HLA-A30,B13,and Cw4 are negatively correlated with ALL,they are possibly the protective genes of ALL.Certain HLA haplotypes are also correlated with ALL occurrence.

关 键 词：急性淋巴细胞白血病 人类白细胞抗原 基因型 基因频率 相对危险率 

分 类 号：R733.71[医药卫生—肿瘤]