IL10-592位点AA基因型对HLA-10／10全相合无关供者异基因造血干细胞移植预后的影响  

Effects of IL10-592 locus of AA genotype on the incidence of aGVHD and survival after HLAmatched unrelated ailogeneic hematopoietic stem cell transplantation

作　　者：杨志洛 邱桥成[1] 丁子轩[1] 潘芝娟[1] 赵勤勤[1] 何军[1] 

机构地区：[1]苏州大学附属第一医院、江苏省血液研究所,215007

出　　处：《中华血液学杂志》2016年第5期372-376,共5页Chinese Journal of Hematology

基　　金：国家自然科学基金（81273226、81072435）;江苏省医学创新团队与领军人才（LJ201138）;江苏省临床医学科技专项（BL2014038、BL2013013）

摘　　要：目的研究供患者IL10基因．592（rs1800872）单核苷酸多态性位点（SNP）不同基因型对HLA全相合无关供者异基因造血干细胞移植（allo—HSCT）预后的影响。方法104对HLA全相合供患者和100名健康人的DNA样本，均采用Sanger法基因测序技术检测IL10-592位点SNP，并结合临床资料分析不同基因型对allo-HSCT各预后因素的影响。结果当供患者IL10—592位点基因型相同且分别为AA／AA、AC／AC、CC／CC时，移植后Ⅲ-Ⅳ度急性移植物抗宿主病（aGVHD）发生率分别为47．1％、3．7％和0，三组间差异有统计学意义（P=0．002）。当供患者IL10—592位点基因型不同，且患者为AA或供者为AA基因型时，不同基因型组合Ⅲ～Ⅳ度aGVHD发生率差异均有统计学意义（P=0．046，P=0．041）。当患者IL10—592位点为AA、AC、CC基因型时，移植后Ⅲ-Ⅳ度aGVHD发生率分别为27．8％、10．2％、11．1％（P=0．072）；肠道aGVHD的发生率分别为22．2％、5．1％、11．1％（P=0．040）；2年总生存（OS）率分别为48．2％、75．1％、85．7％（P=0．002）；2年无病生存（DFS）率分别为48．5％、66．3％、76．2％（P=0．045）。当供者IL10-592位点为AA、AC、CC基因型时，患者Ⅲ～Ⅳ度aGVHD发生率分别为26．5％、8．9％、0（P=0．024）；肠道aGVHD发生率分别为20．4％、4．4％、0（P=-0．026）。多因素分析结果提示患者或供者IL10-592位点AA基因型组移植后有较高Ⅲ。Ⅳ度aGVHD发病风险（OR=3．3，P=0．049；OR=3．9，P=0．043）。而患者或供者IL10—592位点为AA、AC、CC不同基因型时，对慢性GVHD发生率和复发率均无明显影响。结论在HLA．10／10全相合无关供者allo—HSCT中，患者和（或）供者IL10—592位点AA基因型是allo—HSCT后发生较高Ⅲ-Ⅳ度aGVHD和较低OS、DFS率的不利因素。Objective To explore the impact of IL10-592 （rs1800872）single nucleic acid polymorphism （SNP） on the prognosis of HLA matched unrelated hematopoietic stem cell transplantation （HSCT）. Methods The polymorphism of IL10- 592 in 104 recipientdonor pairs and 100 healthy volunteers was analyzed with sequence based typing （SBT）. Results When the genotype of IL10-592 in donors and recipients matched, AA/AA genotype had higher incidence of Ⅲ- ⅣaGVHD than AC/AC or CC/CC genotype （47.1%, 3.7%, 0, P=0.002）. When the genotype of IL10-592 in donors and recipients mismatched, recipients with AC genotype or donors with AA genotype, there was significant different incidence ofⅢ- Ⅳ aGVHD among donors or recipients with different genotype （P=0.046, P=0.041 ）. The recipients with AA genotype had higher incidence of Ⅲ- ⅣaGVHD than AC or CC genotype （27.8% vs 10.2%, 11.1%; P=-0.072）, and higher incidence of intestinal aGVHD （22.2%vs 5.1%,11.1%; P=0.040） , lower incidence of 2-year overall survival （OS： 48.2% vs 75.1%, 85.7%; P=-0.002）, lower incidence of 2 year disease free survival （DFS： 48.5% vs 66.3%, 76.2%; P=0.045 ）. Patients had higher incidence ofⅢ- Ⅳ aGVHD with donors of AA genotype than with donors of AC or CC genotype （26.5% vs 8.9%, 0; P= 0.024）, and higher incidence of intestinal aGVHD （20.4% vs 4.4%, 0; P=0.026）. In multivariate analysis, the genotype of IL10-592AA in recipients and donors had increased risk of Ⅲ- ⅣaGVHD （OR=3.3, P= 0.049 ; 0R=3.9, P=-0.043）. There were no statistical differences on the incidence of cGVHD and relapse. Conclusion In HLA-10/10 matched unrelated HSCT, the presence of IL10-592 AA genotype in recipients and/or donors is an adverse factor for Ⅲ- ⅣaGVHD, worse OS and 2-year DFS.

关 键 词：白细胞介素10 单个核苷酸多态性 造血干细胞移植 移植物抗宿主病 总体 生存 无病生存 

分 类 号：R457.7[医药卫生—治疗学]