南方汉族KIR-HLA系统基因多态性与慢性髓系白血病的相关性  

Association of genetic polymorphisms of KIR-HLA system with chronic myeloid leukemia among ethnic Hans from southern China

作　　者：邓志辉[1] 甄建新[1] 王大明[1] 何柳媚[1] 邹红岩[1] 

机构地区：[1]广东省深圳市血液中心免疫遗传研究室,518035

出　　处：《中华医学遗传学杂志》2017年第1期53-57,共5页Chinese Journal of Medical Genetics

基　　金：国家自然科学基金（81373158）

摘　　要：目的探讨中国南方汉族人群KIR-HLA系统基因多态性与慢性髓系白血病（chronic myeloid leukemia，CML）的相关性。方法对172份成年CML患者及480份随机正常对照的样本，采用PCR-SSP方法检测K豫基因，用测序分型法进行HLA-A、-B、-C基因分型。从K豫基因及其基因组合型、HLAI类配体、已知的单个KIR4-HLA受一配体组合及KIR-HLA基因型组合等4个层次比较病例组与对照组分子遗传多态性的差异。结果与KIR2DL1配位的HLA-C2、KIR2DL1＋HLA-C2、与KIR3DL1配位的HLA—BBw4—80I的检出频率均显著低于正常对照组，为CML保护因素（HLA-C2：OR=0．386，95％CI：0．240-0．620，P〈0．01；KIR2DL1＋HLA-C2：OR=0．316，95％CI：0．191～0．525，P〈0．01；HLA-BBw4—80I：OR=0．576，95％CI：0．384～0．862，P〈0．01）。HLA-C2及HLA—BBw4—801分子表达机率降低，可能导致与相应的抑制性KIR亲和力的减弱，有利于NK细胞活化。最值得注意的是：KIR-HLA基因型组合ID2（KIRAA1-HLA-C1／C1-Bw6／Bw6-A3／11）在CML组的检出频率显著高于正常对照组，为CML易感因素（OR=2．163，95％CI：1．198～3．906，P〈0．01）。结论本研究识别了KIR-HLA与CML白血病相关的易感或保护性因素，可为CML白血病的发病机制和个体化免疫治疗提供新的线索及理论依据。Objective To explore the association of KIR-HLA gene polymorphism with chronic myeloid leukemia （CML） among ethnic Hans from southern China. Methods A total of 172 adult CML patients and 480 unrelated healthy controls were screened for the presence of KIR with sequence-specific primers-PCR （PCR-SSP） and sequence-based typing （SBT） of HLA-A, -B and -C loci. Polymorphisms of the KIR-HLA system were analyzed at 4 levels, and the frequencies of KIR framework genes and KIR profiles, class I HLA ligands, matched KIR＋HLA pairs and KIR-HLA compound profile were compared between the two groups. P values were calculated using SPSS 13.0 software. Results For the CML group, the frequencies of HLA-C2 ligand, 2DL1 d-HLA-C2 pair and HLA-B Bw4-80I were significantly lower than those of the control group, suggesting a protective effect against CML （HLA-C2： OR ： 0. 386, 95 % CI： 0. 240-0. 620, P〈0.01; 2DLI＋HLA-C2： OR=0. 316, 95 %CI：0. 191-0. 525, P〈0.01; HLA-B Bw4-80I： OR= 0. 576, 95% CI： 0. 384-0. 862, P〈 0. 01）. The frequencies of KIR2DL1 ligand （HLA-C2） and KIR3DL1 ligand （HLA-B Bw4-80I） in the CML group were significantly lower than that of the control group, suggesting that the HLA-C2 and HLA-B Bw4-80I expression is probably decreased in the CML patient group, which led to reduced inhibitory signal and enhanced activating signal of KIR2DL1＋ and/or KIR3DL1＋ NK cells. Notably, the frequency of KIR-HLA compound profiles ID2 （KIR AA1-HLA-C1/C1- Bw6/Bw6-A3/11） in CML patients significantly increased in the CML patient group compared with the control group, suggesting that the KIR-HLA compound profiles ID2 may be a risk factor for CML （OR=2. 163, 95%CI 1. 198-3. 906, P〈0.01）. Conclusion Above analysis has identified certain protective and risk factors for CML from the KIR-HLA system, which may provide a clue for the pathogenesis of leukemia and development of individualized immune therapy.

关 键 词：杀伤细胞免疫球蛋白样受体 人类白细胞抗原 遗传多态性 慢性髓系白血病 中 国南方汉族 

分 类 号：R733.72[医药卫生—肿瘤]