文章：

宿主免疫遗传变异影响急性髓系白血病的发病风险：NuCLEAR联盟研究结果

Host immune genetic variations influence the risk of developing acute myeloid leukaemia: results from the NuCLEAR consortium

原文发布日期：2020-07-16

DOI: 10.1038/s41408-020-00341-y

类型: Article

开放获取: 是

英文摘要：

The purpose of this study was to conduct a two-stage case control association study including 654 acute myeloid leukaemia (AML) patients and 3477 controls ascertained through the NuCLEAR consortium to evaluate the effect of 27 immune-related single nucleotide polymorphisms (SNPs) on AML risk. In a pooled analysis of cohort studies, we found that carriers of the IL13rs1295686A/A genotype had an increased risk of AML (PCorr = 0.0144) whereas carriers of the VEGFArs25648T allele had a decreased risk of developing the disease (PCorr = 0.00086). In addition, we found an association of the IL8rs2227307 SNP with a decreased risk of developing AML that remained marginally significant after multiple testing (PCorr = 0.072). Functional experiments suggested that the effect of the IL13rs1295686 SNP on AML risk might be explained by its role in regulating IL1Ra secretion that modulates AML blast proliferation. Likewise, the protective effect of the IL8rs2227307 SNP might be mediated by TLR2-mediated immune responses that affect AML blast viability, proliferation and chemorresistance. Despite the potential interest of these results, additional functional studies are still warranted to unravel the mechanisms by which these variants modulate the risk of AML. These findings suggested that IL13, VEGFA and IL8 SNPs play a role in modulating AML risk.
 

摘要翻译： 

本研究旨在通过NuCLEAR联盟确定的654例急性髓系白血病（AML）患者和3477例对照者，开展两阶段病例对照关联研究，评估27个免疫相关单核苷酸多态性（SNP）对AML风险的影响。在队列研究的汇总分析中，我们发现携带IL13rs1295686 A/A基因型者AML风险增加（校正P值=0.0144），而携带VEGFArs25648 T等位基因者患病风险降低（校正P值=0.00086）。此外，我们发现IL8rs2227307 SNP与AML发病风险降低相关，该关联经过多重检验后仍保持边际显著（校正P值=0.072）。功能实验表明，IL13rs1295686 SNP对AML风险的影响可能通过其调节IL1Ra分泌的机制实现，进而调控AML原始细胞增殖。同样，IL8rs2227307 SNP的保护作用可能是通过TLR2介导的免疫反应影响AML原始细胞活力、增殖及化疗耐药性来实现。尽管这些结果具有潜在价值，但仍需进一步的功能研究来阐明这些遗传变异调节AML风险的具体机制。本研究提示IL13、VEGFA和IL8基因多态性在调节AML风险中发挥重要作用。

原文链接：

Host immune genetic variations influence the risk of developing acute myeloid leukaemia: results from the NuCLEAR consortium