Table_1_The association between genetic variants at 3’-UTR and 5’-URR of HLA-G gene and the clinical outcomes of patients with leukemia receiving hematopoietic stem cell transplantation.doc

In addition to the classical human leukocyte antigen (HLA) genes, the outcomes of post-hematopoietic stem cell transplantation (HSCT) are associated with human leukocyte antigen (HLA)-related genes and non-HLA genes involved in immune regulation. HLA-G gene plays an important role in immune tolerance, assisting immune escape of tumor cells, and decrease of transplant rejection. In this study, we explored the association of genetic variants at the 3’-untranslated region (3’-UTR) and 5’-upstream regulatory region (5’-URR) of HLA-G gene with the adverse outcomes of patients with leukemia receiving HSCT. The genomic DNAs of 164 patients who had acute leukemia and received HSCT were collected for analysis. Nine single nucleotide polymorphisms (SNPs) and six haplotypes in the 3’-UTR and 27 SNPs and 6 haplotypes in the 5’-URR were selected to investigate their relationship with the development of adverse outcomes for patients receiving HSCT, including mortality, relapse, and graft-versus-host disease. Our results revealed that two SNPs (rs371194629 and rs9380142) and one haplotype (UTR-3) located in the 3’-UTR and two SNPs (rs3823321 and rs1736934) and one haplotype (G0104a) located in the 5’-URR of HLA-G were associated with the occurrence of chronic GVHD or development of any forms of GVHD. No SNP was found to associate with the occurrence of mortality and relapse for patients receiving HSCT. These SNPs and haplotypes may play important roles in regulating immune tolerance of allografts post-HSCT that can be used to predict the risk of poor outcomes after receiving HSCT and giving preventive treatment to patients on time.

除经典人类白细胞抗原（human leukocyte antigen, HLA）基因外，造血干细胞移植（hematopoietic stem cell transplantation, HSCT）后的转归还与HLA相关基因以及参与免疫调控的非HLA基因密切相关。HLA-G基因在免疫耐受、辅助肿瘤细胞免疫逃逸以及降低移植排斥反应中发挥重要作用。本研究探讨了HLA-G基因3'非翻译区（3'-untranslated region, 3'-UTR）与5'上游调控区（5'-upstream regulatory region, 5'-URR）的遗传变异与急性白血病患者接受HSCT后不良预后的关联。本研究收集了164例确诊急性白血病并接受HSCT的患者的基因组DNA进行分析。研究选取了3'-UTR区域的9个单核苷酸多态性（single nucleotide polymorphisms, SNPs）与6个单倍型，以及5'-URR区域的27个SNPs与6个单倍型，以探究其与HSCT患者不良预后（包括死亡、复发及移植物抗宿主病（graft-versus-host disease, GVHD））发生发展的关联。研究结果显示，位于HLA-G基因3'-UTR区域的2个SNPs（rs371194629、rs9380142）与1个单倍型（UTR-3），以及位于5'-URR区域的2个SNPs（rs3823321、rs1736934）与1个单倍型（G0104a），均与慢性GVHD的发生或各类GVHD的进展显著相关。未发现与HSCT患者死亡及复发风险相关的SNPs。上述SNPs与单倍型可能在调控HSCT后同种异体移植物的免疫耐受中发挥关键作用，可用于预测HSCT术后不良预后风险，并及时为患者提供预防性干预治疗。