Department of Genetic Epidemiology, University Medical Center, Georg August University Göttingen, Göttingen, Germany.
Translational & Clinical Research Institute, Faculty of Medical Science, Medical School, Newcastle University, Newcastle upon Tyne, United Kingdom.
Front Immunol. 2024 Feb 7;15:1280876. doi: 10.3389/fimmu.2024.1280876. eCollection 2024.
Data on genomic susceptibility for adverse outcomes after hematopoietic stem cell transplantation (HSCT) for recipients are scarce.
We performed a genome wide association study (GWAS) to identify genes associated with survival/mortality, relapse, and severe graft-versus-host disease (sGvHD), fitting proportional hazard and subdistributional models to data of n=1,392 recipients of European ancestry from three centres.
The single nucleotide polymorphism (SNP) rs17154454, intronic to the neuronal growth guidant semaphorin 3C gene (, was genome-wide significantly associated with event-free survival (p=7.0x10) and sGvHD (p=7.5x10). Further associations were detected for SNPs in the Paxillin gene ( death without prior relapse or sGvHD, as well as for SNPs of the Plasmacytoma Variant Translocation 1 gene , a long non-coding RNA gene, the Melanocortin 5 Receptor and the WW Domain Containing Oxidoreductase gene (, all associated with the occurrence of sGvHD. Functional considerations support the observed associations.
Thus, new genes were identified, potentially influencing the outcome of HSCT.
关于造血干细胞移植（HSCT）受者不良结局的基因组易感性数据很少。
我们进行了全基因组关联研究（GWAS），以确定与生存/死亡率、复发和严重移植物抗宿主病（sGvHD）相关的基因，对来自三个中心的 1392 名欧洲血统受者的数据拟合比例风险和亚分布模型。
单核苷酸多态性（SNP）rs17154454 位于神经元生长导向信号素 3C 基因（内，与无事件生存（p=7.0x10）和 sGvHD（p=7.5x10）显著相关。在 Paxillin 基因（rs7016873）中检测到与死亡无关的 SNP，没有先前的复发或 sGvHD，以及 Plasmacytoma Variant Translocation 1 基因（rs7515975）的 SNP，长非编码 RNA 基因（rs7576367），黑色素皮质素 5 受体（rs737235）和 WW 结构域包含氧化还原酶基因（rs12195473），所有这些都与 sGvHD 的发生有关。功能考虑支持观察到的关联。
因此，鉴定了新的基因，这些基因可能影响 HSCT 的结果。
