Abstract
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。
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