allo-HSCT受者细胞因子基因多态性与急性移植物抗宿主病的关系

Correlation between cytokine gene polymorphism and aGVHD in allo-HSCT recipients

目的:探讨在异基因造血干细胞移植(allo-HSCT)中肿瘤坏死因子α(TNF-α)、白细胞介素6(IL-6)、白细胞介素10(IL-10)、转化生长因子β1(TGF-β1)、干扰素γ(IFN-γ)等多种疾病相关细胞因子基因多态性与急性移植物抗宿主病(aGVHD)的相互关系。方法:选取2014年1月至2015年12月进行allo-HSCT的受者32例及正常人群36例作为研究对象,采用聚合酶链式反应(PCR)联合基因测序对目的基因特殊SNP位点基因分型进行检测,观察受者术后出现aGVHD的不同情况,分析细胞因子基因多态性对allo-HSCT预后的影响,探讨疾病相关细胞因子特殊SNP点突变与a GVHD发病严重程度的潜在相关性。结果:在全部allo-HSCT受者中,TNF-α-308(G/A)、IL-6-174(G/C)、IL-10-1082(A/G)、TGF-β1+915(G/C)、IFN-γ+874(T/A)等细胞因子的基因多态性分布与重度aGVHD的发生率未见有显著性的差异(P>0.05)。在TGF-β1+869SNP位点上,C/T型allo-HSCT患者中重度a GVHD发病率显著高于C/C、T/T两个基因型患者组(P<0.01)。结论:在allo-HSCT患者中TGF-β1+869(C/T)基因多态性与a GVHD发病的严重程度具有密切联系。C/T型allo-HSCT患者更容易发生重度aGVHD,是诱发严重aGVHD出现的潜在危险因素。因此,在allo-HSCT患者中针对TGF-β1+869(C/T)进行基因多态性检测,制定合理的aGVHD预防方案,可能有助于减少减轻aGVHD的发生。

Objective： To investigate the relationship between gene polymorphisms of disease-relevant multiple cytokines including TNF-α,IL-6,IL-10,TGF-β1,IFN-γ and acute graft versus host disease（ a GVHD） in allogeneic hematopoietic stem cell transplantation（ allo-HSCT）. Methods： 32 cases of recipients received allo-HSCT and 36 cases of normal groups in January 2014 to December2015 were selected as objects of study. We detected genotypes on specific SNP of target genes by polymerase chain reation（ PCR） combined with gene sequencing and observed the occurrence of aGVHD in postoperative recipients. The influence of cytokine gene polymorphisms on prognosis of allo-HSCT patients was analyzed,and the potential relationship between specific SNP mutation of the disease-relevant cytokine genes and severity of aGVHD was discussed. Results： Distribution of cytokines gene polymorphism including TNF-α-308（ G/A）,IL-6-174（ G/C）,IL-10-1082（ A/G）,TGF-β1＋915（ G/C）,IFN-γ（ T/A） had no significant differences with incidence of severe a GVHD（ P〈0. 05）. However,the occurrence of severe a GVHD in allo-HSCT recipients with C / T genotype was significantly higher than C / C and T / T in SNP of TGF-β1＋869（ P〈0. 01）. Conclusion： Gene polymorphism of TGF-β1＋869（ C / T） in allo-HSCT patients was closely related to the occurrence of severe aGVHD. The research show allo-HSCT patients with C / T genotype occurred severe aGVHD more frequently,which is an important potential risk factor to induce the incidence of severe a GVHD. Therefore,detecting gene polymorphism of TGF-β1＋869（ C / T） in allo-HSCT recipients and developing the appropriate therapeutic regimen may be helpful to reduce the incidence of aGVHD.