Karimi Mohammad Hossein, Daneshmandi Saeed, Pourfathollah Ali Akbar, Geramizadeh Bita, Ramzi Mani, Yaghobi Ramin, Ebadi Padideh
Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
Exp Clin Transplant. 2010 Jun;8(2):125-9.
Analysis of nonhistocompatibility leucocyte antigen functional genomics in stem cell transplant can lead to prediction of clinical outcomes in histocompatibility leucocyte antigen-matched sibling-transplant recipients. Some of the cytokine gene polymorphisms might be associated with severe, acute graft-versus-host disease after allogeneic stem cell transplant. We evaluated gene polymorphisms of IL-6 G-174C, TGF-beta T+869C, IL-4 C-590T, and IFN-alpha T+874A cytokines in bone marrow transplant patients.
The amplification refractory mutation system-polymerase chain reaction ARMSPCR method was used to characterize IL-6 G-174C, TGF-beta T+869C, and IFN-alpha T+874A polymorphisms, and PCR-RFLP, using AvaII restriction enzyme, was done for IL-4 C-590T characterization in 35 bone marrow transplant patients. Acute graft-versus-host disease episodes were diagnosed according to EMBT criteria.
Analysis showed that IFN-alpha +874T allele (P = .027, OR=0.198, 95% CI=0.049-0.801) was correlated to moderate-to-severe graft-versus-host disease. TGF-beta T+869C, IFN-alpha T+874A, IL-6 G-174C and IL-4 C-590T frequencies were not significantly different in the 2 graft-versus-host disease severity groups (P > .05).
According to the results, we concluded that the IFN-alpha T+874A gene polymorphism has a predictive value for severity of graft-versus-host disease after bone marrow transplant. High producer genotypes of IFN-alpha are genetic risk factors for development of graft-versus-host disease.
分析干细胞移植中的非组织相容性白细胞抗原功能基因组学，有助于预测人类白细胞抗原匹配的同胞移植受者的临床结局。某些细胞因子基因多态性可能与异基因干细胞移植后严重的急性移植物抗宿主病相关。我们评估了骨髓移植患者中白细胞介素6（IL-6）G-174C、转化生长因子β（TGF-β）T+869C、白细胞介素4（IL-4）C-590T和干扰素α（IFN-α）T+874A细胞因子的基因多态性。
采用扩增阻滞突变系统-聚合酶链反应（ARMS-PCR）方法对IL-6 G-174C、TGF-β T+869C和IFN-α T+874A多态性进行鉴定，并使用AvaII限制性内切酶通过聚合酶链反应-限制性片段长度多态性（PCR-RFLP）对35例骨髓移植患者的IL-4 C-590T进行鉴定。根据欧洲骨髓移植协作组（EMBT）标准诊断急性移植物抗宿主病发作。
分析显示，IFN-α +874T等位基因（P = 0.027，OR = 0.198，95%CI = 0.049 - 0.801）与中重度移植物抗宿主病相关。TGF-β T+869C、IFN-α T+874A、IL-6 G-174C和IL-4 C-590T频率在两个移植物抗宿主病严重程度组中无显著差异（P > 0.05）。
根据结果，我们得出结论，IFN-α T+874A基因多态性对骨髓移植后移植物抗宿主病的严重程度具有预测价值。IFN-α的高产生基因型是移植物抗宿主病发生的遗传危险因素。
