摘要
目的 研究中国南方汉族人群中KIR2DS4等位基因分布及2DS4基因对无关供者全相合造血干细胞移植（HSCT）的影响.方法 采用基因测序（Sequenee-based testing,SBT）和TOPO-TA 克隆相结合的方法 ,对接受HSCT的75对HLA-A、-B、-Cw、-DRB1、-DQB1高分辨全相合的供、受者进行KIR2DS4等位基因分型,150名供、受者均为中国南方汉族人群,75例受者中急性淋巴细胞白血病（ALL）29例,慢性粒细胞白血病（CML）24例,急性髓系白血病（AML）19例,其他恶性血液病3例.结果 150名供、受者中139例（92.7%）存在KIR2DS4基因,对2DS4基因全长测序后发现4个2DS4等位基因：KIR2DS4＊00101、＊003、＊004和＊007;109例（78.4%）存在2DS4＊00101;2DS4缺失型（具有1个或缺失2DS4＊00101基因）与完整型（具有两个2DS4＊00101基因）的存在比率为1：2;发现3个KIR2DS4新基因.当供者KIR分型为B/x（40例）时,移植后总体生存率明显高于供者为A/A组（35例）[RR=3.1（95%CI 1.1～8.6）,P=0.007];当供者为完整型（36例）时,移植后总体生存率低于供者为缺失型（39例）（P=0.031）;在A/A组中,当供者为完整型（14例）时,移植后急性移植物抗宿主病（GVHD）的发生率明显高于供者为缺失型（21例）[RR=9.0（95%CI 1.2～66.9）,P=0.010],并以Ⅲ～Ⅳ度aGVHD尤为明显（P=0.006）.结论 SBT与TOPO-TA基因克隆的高分辨分型方法可用于研究KIR基因家族多态性,并且移植前在HLA分型的基础上对供受者进行KIR2DS4基因分型,可能对临床选择合适的供者提供有利的依据.
Objective To detect the frequencies of KIR2DS4 alleles in Chinese Han population and to study the impact of KR2DS4 alleles on clinical outcomes of HLA identical unrelated allo-HSCT. Methods A Sequence-Based Testing （SBT） and TOPO TA cloning system for identifying and distinguishing alleles of the KIR2DS4 gene were established. A total of 150 Chinese-Han individuals, including 75 leukemia patients who received allo-HSCT and their HLA high-resolution typing identical unrelated donors （URD） were entered this study. The patients underwent transplantation for CML （n=24）, AML （n = 19）, ALL （n =29） and other malignancies （n=3）. Results The majority （139） of the 150 samples （92.7%） were positive for KIR2DS4. Sequencing of the whole length coding region of this gene identified four of the 12 known KIR2DS4 alleles, KIR2DS4 ＊00101, ＊003, ＊004, and ＊007. 2DS4 ＊00101 was the most frequent, being found in 109 of the 139 individuals （78.4%）. The ratio of deleted to non-deleted versions of KIR2DS4 was approximately 1：2. Three novel KIR2DS4 alleles were identified. Transplantations from KIR haplotype B/x donors showed significantly higher overall survival rates than those from KIR haplotype A/A donors [ RR 3.1 （95%CI 1.1 - 8.6）, P = 0.007 ]. There was a lower overall survival rates in recipients when their donors carried two 2DS4 full-length allele （2DS4＊001） than those carried less （0 or 1） 2DS4 ＊001 allele （P=0.031）.In the haplotype A/A group, a higher risk of acute GVHD （aGVHD） [ RR 9.0 （95 % CI 1.2 - 66.9）, P =0.01 ], especially grade Ⅲ - Ⅳ aGVHD （ P = 0. 006 ）, was seen when the donor was homozygous for the full-length KIR2DS4 ＊ 00101 allele. Conclusion The development and application of the described SBT 2DS4 allele typing method highlights the diverse nature of the KIR gene family and displays the existence of KIR polymorphism that remains uncharacterized. Our findings suggest that KIR typing for 2DS4 be beneficial for selecting suitable
出处
《中华血液学杂志》
CAS
CSCD
北大核心
2010年第11期726-731,共6页
Chinese Journal of Hematology
基金
卫生部科研基金（wkj2006-2-023）
江苏省高校自然基金（07kj320106）
江苏省六大人才高峰（07-B-21）
苏州市基础设施项目（SZS0702）
