RNA N^(6)-甲基腺苷甲基化对老年患者阿司匹林反应性的影响

Effect of RNA m^(6)A methylation on aspirin responsiveness in elderly patients

目的探讨RNA N^(6)-甲基腺苷(m^(6)A)甲基化水平及相关基因对老年患者阿司匹林反应性的影响。方法纳入规律服用阿司匹林100 mg/d的老年患者34例,根据光比浊法检测花生四烯酸诱导的血小板聚集率分为低反应组14例(血小板聚集率>12%),高反应组20例(血小板聚集率<7%)。检测全血RNA m^(6)A甲基化水平及相关基因(YTHDF1、METTL3等)表达,血浆前列腺素H2和血栓素B2水平。结果低反应组全血RNA m^(6)A甲基化水平明显高于高反应组,差异有统计学意义(P<0.05)。低反应组YTHDF1和METTL3 mRNA表达明显高于高反应组[2.77(1.25,4.61)vs 1.32(0.75,1.84),P<0.05;1.64(1.01,2.92)vs 0.80(0.57,1.26),P<0.01]。低反应组血浆前列腺素H2和血栓素B2水平明显高于高反应组[(180.21±15.12)ng/L vs(136.48±9.32)ng/L,(213.44±10.83)ng/L vs(177.27±9.90)ng/L,P<0.05]。结论RNA m^(6)A甲基化水平在阿司匹林低反应性老年患者中升高,检测相关基因可为阿司匹林抗血小板的个体化治疗提供依据。

Objective To investigate the effect of RNA m^(6)A methylation level and related genes on aspirin responsiveness in elderly patients.Methods Thirty-four elderly patients who took aspirin 100 mg/d regularly were enrolled in this study.According to arachidonic acid-induced PAR detected by turbidimetry, they were divided into aspirin hyporesponsive group(PAR>12%,n=14) and aspirin hyperresponsive group(PAR<7%,n=20).The level of RNA m^(6)A methylation and related gene(YTHDF1,METTL3) expression in whole blood and the contents of plasma prostaglandin H2and thromboxane B2were detected.Results The methylation level of RNA m^(6)A was significantly higher in the aspirin hyporesponsive group than the aspirin hyperresponsive group(P<0.05).The aspirin hyporesponsive group had obviously increased mRNA levels of YTHDF1 [2.77(1.25,4.61) vs 1.32(0.75,1.84),P<0.05] and METTL3 [1.64(1.01,2.92) vs 0.80(0.57,1.26),P<0.01],and elevated contents of plasma prostaglandin H2(180.21±15.12 ng/L vs 136.48±9.32 ng/L,P<0.05) and thromboxane B2(213.44±10.83 ng/L vs 177.27±9.90 ng/L,P<0.05) when compared with the aspirin hyperresponsive group.Conclusion The level of RNA m^(6)A methylation is increased in the elderly patients with low response to aspirin.Detection of m^(6)A related genes can provide reference for individualized antiplatelet therapy with aspirin.