药源性急性严重过敏反应（DIA）难以预测且危害严重，DIA患者受组胺、白三烯及更强的过敏介质血小板活化因子（PAF）的影响。我们的研究表明：PAF可激发小鼠典型DIA样表现；既往DIA患者PAF乙酰水解酶（PAF-AH）编码基因的PLA2G7 R92H突变频率显著低于无过敏史者，提示该基因多态性与DIA密切相关，但机制尚不明确。本项目通过二代基因捕获测序技术检测DIA急性期患者PAF信号通路（含PAF-AH）基因多态性，验证PLA2G7 R92H与急性期DIA的相关性，寻找影响DIA的其他可能位点；通过基因编辑技术，在鼠肝实质细胞、肝巨噬细胞中研究PLA2G7 R92H对PAF-AH酶活性的影响；在基因敲入技术制备的PLA2G7 R92H KI小鼠模型中，验证PLA2G7 R92H的功能。研究将揭示PLA2G7 R92H在DIA发生中的作用，为认识和防治DIA的发生提供新的研究证据。

Drug-induced anaphylaxis (DIA) is an unpredictable and severe allergic reaction. Histamine, leukotriene, along with platelet-activating factor acetylhydrolase (PAF), which is the most potent allergic mediator, would have impact on patients undergoing the acute phase of anaphylaxis. Our previous studies have showed that PAF could provoke DIA-like symptoms in mice. And in our latest unpublished study, it has showed that the frequency of R92H polymorphism of the gene encoding platelet-activating factor acetylhydrolase(PLA2G7) was significant lower among patients with DIA history compared to those without allergic history. This indicates that PLA2G7 R92H polymorphism might be highly correlated with DIA. However, the regulatory mechanism of PLA2G7 R92H on DIA remains unknown. This study intends to confirm the correlation between PLA2G7 R92H polymorphism and DIA in patients undergoing the acute phase of anaphylaxis and investigate the relationship between PAF-AH-related genes and the onset of DIA by next generation sequencing. Furthermore, the exact function of PLA2G7 R92H on PAF-AH will be tested in mouse AML12 cells and Kupffer cells by gene editing, and the function of PLA2G7 R92H in DIA will be tested in PLA2G7 R92H KI mice by gene knockin. The potential results of this study will reveal the regulatory mechanism of PLA2G7 R92H on DIA, and provide new experimental evidence and theoretical basis for the mechanism of DIA and DIA treatment.