Piao Zhe, Kim Hyung Joon, Choi Jung Yoon, Hong Che Ry, Lee Ji Won, Kang Hyoung Jin, Park Kyung Duk, Shin Hee Young
Department of Pediatrics, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea; Department of Hematology, Yanbian University Hospital, Yanji, China.
Department of Pediatrics, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
Int Immunopharmacol. 2016 Feb;31:132-9. doi: 10.1016/j.intimp.2015.12.022. Epub 2015 Dec 29.
Forkhead BOX P3 (FOXP3) polymorphisms have recently been investigated as candidate risk factors in several tumors and autoimmune diseases. This study aims to evaluate the potential influence of FOXP3 rs3761548 polymorphism in the donor on the outcome of allogeneic hematopoietic stem cell transplantation (allo-HSCT). A total of 171 patients were enrolled for this study and genotyped using direct sequencing. Patients with rs3761548 CC genotype had higher incidence of hepatic veno-occlusive disease (HVOD) and cytomegalovirus (CMV) infection than that of the individuals with AA or AC genotype (P=0.011, P=0.023). Treatment-related mortality (TRM) rate of patients with AA or AC genotype was lower than that of the patients with CC genotype (P=0.044) resulting in a difference in overall survival (OS). However, there was no difference in graft-versus-host disease (GVHD) relapse or blood stream infection (BSI), depending on the genotype at rs3761548 locus. In multivariate analysis, CC genotype showed as a risk factor in the development of HVOD and CMV infection, with low OS. In conclusion, this is the first report on FOXP3 rs3761548 SNP in allo-HSCT and we suggest that this SNP be considered a candidate marker for predicting the development of HVOD and CMV infection after allo-HSCT.
叉头框蛋白P3（FOXP3）多态性最近已被作为几种肿瘤和自身免疫性疾病的候选风险因素进行研究。本研究旨在评估供体中FOXP3 rs3761548多态性对异基因造血干细胞移植（allo-HSCT）结果的潜在影响。本研究共纳入171例患者，并采用直接测序法进行基因分型。rs3761548 CC基因型患者的肝静脉闭塞病（HVOD）和巨细胞病毒（CMV）感染发生率高于AA或AC基因型个体（P = 0.011，P = 0.023）。AA或AC基因型患者的治疗相关死亡率（TRM）低于CC基因型患者（P = 0.044），导致总生存期（OS）存在差异。然而，根据rs3761548位点的基因型，移植物抗宿主病（GVHD）复发或血流感染（BSI）并无差异。在多变量分析中，CC基因型显示为HVOD和CMV感染发生的风险因素，总生存期较低。总之，这是关于allo-HSCT中FOXP3 rs3761548单核苷酸多态性的首次报告，我们建议将该单核苷酸多态性视为预测allo-HSCT后HVOD和CMV感染发生的候选标志物。
