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

目的:探讨在异基因造血干细胞移植(allo-HSCT)中肿瘤坏死因子琢(TNF )、白细胞介素6(IL-6)、白细胞介素10(IL-10)、转化生长因子茁1(TGF-1)、干扰素酌(IFN )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aGVHD 发病严重程度的潜在相关性。结果:在全部allo-HSCT 受者中,TNF-308(G/ A)、IL-6-174(G/ C)、IL-10-1082(A/ G)、TGF-1+915(G/ C)、IFN +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-1+869SNP 位点上,C/ T 型allo-HSCT 患者中重度aGVHD 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-1+869(C/ T)基因多态性与aGVHD 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-1+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。

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

Objective:To investigate the relationship between gene polymorphisms of disease-relevant multiple cytokines including TNF-,IL-6,IL-10,TGF-1,IFN and acute graft versus host disease(aGVHD) in allogeneic hematopoietic stem cell trans-plantation(allo-HSCT) .Methods:32 cases of recipients received allo-HSCT and 36 cases of normal groups in January 2014 to December 2015 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-308(G/ A),IL-6-174(G/ C),IL-10-1082(A/ G),TGF-1+915(G/ C),IFN (T/ A) had no significant differences with incidence of severe aGVHD(P>0.05).However,the occurrence of severe aGVHD in allo-HSCT recipients with C/ T genotype was significantly higher than C/ C and T/ T in SNP of TGF-1+869(P<0.01).Conclusion:Gene polymorphism of TGF-1+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 aGVHD.Therefore,detecting gene polymorphism of TGF-1 + 869 ( C/ T) in allo-HSCT recipients and developing the appropriate therapeutic regimen may be helpful to reduce the incidence of aGVHD.