GLCCI1 gene body methylation in peripheral blood is associated with asthma and asthma severity.
GLCCI1 gene body methylation in peripheral blood is associated with asthma and asthma severity.
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DOI：
10.1016/j.cca.2021.09.006
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发表时间：
2021-09
期刊：
影响因子：
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通讯作者：
Yuanyuan Jiang;Qiufen Xun;Rongjun Wan;S. Deng;Xinyue Hu;L. Luo;Xiaozhao Li;Juntao Feng
中科院分区：
文献类型：
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作者：
Yuanyuan Jiang;Qiufen Xun;Rongjun Wan;S. Deng;Xinyue Hu;L. Luo;Xiaozhao Li;Juntao Feng
背景和目的表观遗传学改变在哮喘的发生中起一定作用。本研究旨在探讨糖皮质激素诱导转录因子1(GLCCI1)的甲基化状态及其与哮喘和哮喘严重程度的关系。材料与方法采集33例重度哮喘患者、84例轻、中度哮喘患者和79例健康对照的外周血单个核细胞，采用Massarray EPityper Platform(Agena)进行GLCCI1甲基化筛查。结果发现5个GLCCI1甲基化位点与哮喘独立相关(P<0.05)，在哮喘预测中表现良好，最佳曲线下面积(AUC值)为0.846(P<；0.0001)。在哮喘组中，只有一个部位与重度哮喘独立相关。曲线下面积预测重度哮喘与S预测的1个月的用力呼气量相当(AuC值分别为0.865和0.857，p=0.291)。Spearman相关分析表明GLCCI低甲基化与其在哮喘外周血单核细胞中的低表达有关。GLCCI1基因敲除小鼠的RNA测序结果显示，GLCCI1基因缺失可能影响PI3K-Akt和MAPK通路(调整值为0.01)。结论本研究提示哮喘患者某些部位GLCCI1甲基化水平较低。GLCCI1甲基化位点可能有助于检测哮喘和哮喘严重程度。
Background and aimsEpigenetic changes play a role in the occurrence of asthma. In this study, we evaluated the methylation status of glucocorticoid-induced transcript 1 (GLCCI1) and assessed its associations with asthma and asthma severity.Materials and MethodsPeripheral blood mononuclear cells were harvested from 33 severe asthma patients, 84 mild-moderate asthma patients and 79 healthy controls of Han nationality.GLCCI1methylation were screened using the MassArray Epityper platform (Agena). We also conducted mRNA sequencing ofGLCCI1-knockout mice to further explore possible functions of this gene.ResultsWe found 5GLCCI1methylation sites independently correlated with asthma (adjustedp< 0.05) and perform well in asthma prediction with optimum area under the curve (AUC) value was 0.846 (p< 0.0001). In asthmatic group, only one sites independently associates with severe asthma. Area under the curve in predicting severe asthma is comparable with forced expiratory volume in 1 s predicted (AUC 0.865 and 0.857,p= 0.291). Spearman correlate analysis denotedGLCCI1low methylation is associates with its low expression in asthma PBMCs. Its reduced level may influence PI3k-Akt and MAPK pathways by the results of RNA sequencing ofGLCCI1-knockout mice (adjustedpvalue < 0.01).ConclusionsOur research indicates a lowGLCCI1methylation level in asthma with certain sites are lower in severe asthma group. TheseGLCCI1methylation sites may be contributed to detect asthma and asthma severity.