Yuanyuan Jiang1, Qiufen Xun2, Rongjun Wan1, Shuanglinzi Deng1, Xinyue Hu1, Lisha Luo1, Xiaozhao Li3, Juntao Feng4. 1. Department of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China. 2. Department of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; Department of Respiratory Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi, China. 3. Department of Nephrology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China. 4. Department of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China. Electronic address: jtfeng1976@csu.edu.cn.
Abstract
BACKGROUND AND AIMS: Epigenetic 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 METHODS: Peripheral blood mononuclear cells were harvested from 33 severe asthma patients, 84 mild-moderate asthma patients and 79 healthy controls of Han nationality. GLCCI1 methylation were screened using the MassArray Epityper platform (Agena). We also conducted mRNA sequencing of GLCCI1-knockout mice to further explore possible functions of this gene. RESULTS: We found 5 GLCCI1 methylation sites independently correlated with asthma (adjusted p < 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 denoted GLCCI1 low 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 of GLCCI1-knockout mice (adjusted p value < 0.01). CONCLUSIONS: Our research indicates a low GLCCI1 methylation level in asthma with certain sites are lower in severe asthma group. These GLCCI1 methylation sites may be contributed to detect asthma and asthma severity.
BACKGROUND AND AIMS: Epigenetic 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 METHODS: Peripheral blood mononuclear cells were harvested from 33 severe asthma patients, 84 mild-moderate asthma patients and 79 healthy controls of Han nationality. GLCCI1 methylation were screened using the MassArray Epityper platform (Agena). We also conducted mRNA sequencing of GLCCI1-knockout mice to further explore possible functions of this gene. RESULTS: We found 5 GLCCI1 methylation sites independently correlated with asthma (adjusted p < 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 denoted GLCCI1 low 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 of GLCCI1-knockout mice (adjusted p value < 0.01). CONCLUSIONS: Our research indicates a low GLCCI1 methylation level in asthma with certain sites are lower in severe asthma group. These GLCCI1 methylation sites may be contributed to detect asthma and asthma severity.