GLCCI1 gene body methylation in peripheral blood is associated with 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.