The adverse events of haematopoietic stem cell transplantation are associated with gene polymorphism within human leukocyte antigen region

Ding-Ping Chen,Ai-Ling Hour,Ying-Hao Wen,Wei-Tzu Lin,Po-Nan Wang,Wei-Ting Wang,Fang-Ping Hsu

doi:10.1038/s41598-020-79369-w

Abstract

Adverse reactions may still occur in some patients after receiving haematopoietic stem cell transplantation (HSCT), even when choosing a human leukocyte antigen (HLA)-matched donor. The adverse reactions of transplantation include disease relapse, graft-versus-host disease (GVHD), mortality and CMV infection. However, only the relapse was discussed in our previous study. Therefore, in this study, we investigated the correlation between the gene polymorphisms within the HLA region and the adverse reactions of post-HSCT in patients with acute leukaemia (n = 176), where 72 patients were diagnosed with acute lymphocytic leukaemia (ALL) and 104 were acute myeloid leukaemia (AML). The candidate single nucleotide polymorphisms were divided into three models: donor, recipient, and donor-recipient pairs and the data of ALL and AML were analysed individually. Based on the results, we found 16 SNPs associated with the survival rates, the risk of CMV infection, or the grade of GVHD in either donor, recipient, or donor-recipient matching models. In the ALL group, the rs209132 of TRIM27 in the donor group was related to CMV infection (p = 0.021), the rs213210 of RING1 in the recipient group was associated with serious GVHD (p = 0.003), and the rs2227956 of HSPA1L in the recipient group correlated with CMV infection (p = 0.001). In the AML group, the rs3130048 of BAG6 in the donor-recipient pairs group was associated with serious GVHD (p = 0.048). Moreover, these SNPs were further associated with the duration time of survival after transplantation. These results could be applied to select the best donor in HSCT.

Highlights

Adverse reactions may still occur in some patients after receiving haematopoietic stem cell transplantation (HSCT), even when choosing a human leukocyte antigen (HLA)-matched donor
3 SNPs correlated with CMV infection, including of the rs9282369 of the HLA-DOA gene (p = 0.014), the rs2227956 of HSPA1L gene (p = 0.001) and the rs3130048 of the BAG6 gene (p = 0.035)
For the donor-recipient pairs group, only the rs209130 of TRIM27 gene was related to the risk of graft-versus-host disease (GVHD) grade 3–4 (p = 0.036), in which the matched gene polymorphism of rs209130 in donorrecipient pairs had a lower probability for getting grade[3,4] GVHD than those who were unmatched (OR = 0.333, 95% CI 0.117–0.946)

Summary

Introduction

Adverse reactions may still occur in some patients after receiving haematopoietic stem cell transplantation (HSCT), even when choosing a human leukocyte antigen (HLA)-matched donor. In 2013, Petersdorf et al demonstrated that several SNPs in non-classical HLA genes could potentially affect the effectiveness of H SCT9 We used these SNPs (rs2244546, rs394657, rs429916, rs915654, rs2075800, rs2242656, rs107822, rs209130 and rs2071479) as sourced SNPs to look for candidate SNPs, which were within the 500 bp flanking genomic regions of these sourced SNPs. In our previous studies, we investigated the correlation between these candidate SNPs and disease relapse of post-HSCT, and the results had been reported in peerj (2018)[10] and scientific reports (2019)[11], respectively. We investigated the correlation between these candidate SNPs and disease relapse of post-HSCT, and the results had been reported in peerj (2018)[10] and scientific reports (2019)[11], respectively These studies supported that the outcomes of allo-HSCT might be affected by genes within the HLA system besides HLA-A, -B, -C, -DR and -DQ

Methods

Results

Conclusion