中国汉族人群KIR2DL1高分辨等位基因分布频率及识别HLA—C配体的特点  

The characteristics of frequency distribution of KIR2DL1 alleles polymorphism and recognition HLA-C ligand in the Chinese Han population

作　　者：王苗[1] 何军[1] 鲍晓晶[1] 邱桥成[1] 李杨[1] 徐超[1] 袁晓妮[1] 李翎婕 

机构地区：[1]苏州大学附属第一医院、江苏省血液研究所,215006

出　　处：《中华血液学杂志》2013年第12期1038-1043,共6页Chinese Journal of Hematology

基　　金：国家自然科学基金（81072435、81273266）;江苏省医学创新团队与领军项目（LJ201138）;江苏省临床医学中心研究基金（ZX201102、XK201151）;卫生部重大科研基金（LW201002）;江苏省科技支撑计划项目（BE2010651）;苏州市科技基础设施建设计划项目和中外合作项目（SZS201001、SH201118）

摘　　要：目的研究中国汉族人群KIR2DL1高分辨等位基因频率及识别HLA-C配体的分布特点。方法采用基因测序和序列特异性引物聚合酶链反应（PCR—SSP）方法，对中华骨髓库登记的111例患者和116名无关供者，共计227份样本进行KIR2DL1高分辨等位基因分型和KIR基因分型，有105例患者接受异基因造血干细胞移植（allo—HSCT）。结果227份样本中有224份（98．68％）样本存在KIR2DL1基因，在448个等位基因中共发现3种KIR2DL1＊00302、＊00201、＊00401等位基因多态性，基因表型频率分别为84．82％（380／448）、12．05％（54／448）和3．13％（14／448），等位基因频率分别为61．04％、6．22％、1．58％，并与欧美人种基因频率分布差异有统计学意义。在6种KIR2DL1高分辨等位基因组合中KIR2DL1＊00302、00302（74．55％）纯合组合为最常见的基因型，且KIR2DL1＊00302、00401组合频率在A／A和B／x中的分布差异有统计学意义（P=0．001），含KIR2DLI＊00401的等位基因组合在A／A中无基因频率分布。KIR2DL1＊00302和KIR2DL1＊00201分别均与KIR2DS1、KIR2DL3、KIR2DS4和KIR3DL1／S1有连锁关系（P〈0．001）。在allo—HSCT的KIR／HLA受配体模式中KIR2DL1＊00302与HLA—C2组位点存在相关性，且与HLA—C＊06：02是最常见的识别受配体组合，而与HLA-C＊01：02受配体模式是最常见的产生异源反应活性的组合，二者在受配体模式中的分布差异具有统计学意义（P〈0．05）。结论KIR2DLI＊00302是中国汉族人群中最常见的等位基因，KIR2DLl高分辨基因分型可预测移植后供者NK细胞的异源反应活性并有利于供者的筛选。Objective To find out the distributed characteristics of KIR2DL1 alleles frequencies and the recognition HLA-C ligand in the Chinese Han population. Methods The 111 patients and 116 donors from CMDP were performed the KIR2DL1 high-resoluction typing and KIR genotyping using sequence-based testing （SBT） and PCR-SSP methods. Results A total of 224 individuals with KIR2DL1 locus was predominantly observed and accounted for 98.68% （224/227）. There were 3 different KIR2DLI alleles, including KIR2DLI＊00302, ＊00201 and ＊00401 alleles polymorphism. The most common phenotype observed were KIR2DL 100302 （84.82%, 380/448）, KIR2DL 1＊00201 （12.05%,54/448） and KIR2DLI＊00401 （3.13%,14/448）, present at allele genetype frequencies of 61.04%,6.22% and 1.58% respectively. The allele homozygotic types of KIR2DLI＊00302 and KIR2DL1＊00302 were the most frequent in 6 KIR2DL 1 allele by high resolution typing. The allele heterozygous types of KIR2DL 1＊00302 and KIR2DL 1＊00401 presented statistically different in haplotypes A/A and B/x （P-0.001 ）, and KIR2DL 1＊00401 lacked of all A/A haplotype. The KIR2DLI＊00302 and KIR2DLI＊00201 allele had significant positive associations between different KIR pairs of KIR2DS1, KIR2DL3, KIR2DS4 and KIR3DL1/S1 using linkage diseduilibrium analysis （P 〈 0.01 ）, respectively. In the receptor-ligand of KIR/HLA model after allo-HSCT, KIR2DL 1＊00302 alleles correlated with their HLA-C2 group ligands. KIR2DLl＊00302 and HLA-C＊06：02 was the most common combination ligand model, but KIR2DLI＊00302 and HLA-C＊01：02 was the most frequent mismatch ligand model with the development of NK cell-induced alloreactivity, meanwhile there was statistically significant difference of frequency distribution （P〈 0.05）. Conclusion The KIR2DL1＊00302 was the most frequent allele in Chinese Han population. The KIR2DL1 high resolution typing would be beneficial for predicting donor NK cells alloactivity after hematopoietic stem cell transplantation and selecti

关 键 词：自然杀伤T细胞 受体 KIR KIR2DL1 HLA抗原 基因连锁 

分 类 号：R394[医药卫生—医学遗传学]