Aberrant Methylation of Aging-Related Genes in Asthma

Yu Yang; Lin Yuan; Ming Yang; Xizi Du; Ling Qin; Leyuan Wang; Kai Zhou; Mengping Wu; Ruoxi He; Juntao Feng; Yang Xiang; Xiangping Qu; Huijun Liu; Xiaoqun Qin; Chi Liu

doi:10.3389/fmolb.2021.655285

Aberrant Methylation of Aging-Related Genes in Asthma

Front Mol Biosci. 2021 May 25:8:655285. doi: 10.3389/fmolb.2021.655285. eCollection 2021.

Authors

Yu Yang^{1

2

3}, Lin Yuan², Ming Yang⁴, Xizi Du², Ling Qin^{1

3}, Leyuan Wang², Kai Zhou², Mengping Wu², Ruoxi He^{1

3}, Juntao Feng^{1

3}, Yang Xiang², Xiangping Qu², Huijun Liu², Xiaoqun Qin², Chi Liu^{1

2

5}

Affiliations

¹ Department of Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, Xiangya Hospital, Central South University, Changsha, China.
² Department of Physiology, School of Basic Medicine Science, Central South University, Changsha, China.
³ Basic and Clinical Research Laboratory of Major Respiratory Diseases, Central South University, Changsha, China.
⁴ Centre for Asthma and Respiratory Disease, School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, University of Newcastle and Hunter Medical Research Institute, Callaghan, NSW, Australia.
⁵ Research Center of China-Africa Infectious Diseases, Xiangya School of Medicine Central South University, Changsha, China.

Abstract

Background: Asthma is a complex pulmonary inflammatory disease which is common among older adults. Aging-related alterations have also been found in structural cells and immune cells of asthma patients. Nonetheless, the underlying mechanism by which differenced aging-related gene contributes to asthma pathology remains unclear. Of note, DNA methylation (DNAm) has been proven to play a critical mechanism for age-related gene expression changes. However, the methylation changes of aging-related genes in asthma patients are still obscure. Methods: First, changes in DNAm and gene expression were detected with multiple targeted bisulfite enrichment sequencing (MethTarget) and qPCR in peripheral blood of 51 healthy controls (HCs) and 55 asthmatic patients. Second, the correlation between the DNAm levels of specific altered CpG sites and the pulmonary function indicators of asthma patients was evaluated. Last, the receiver operator characteristic (ROC) curve and principal component analysis (PCA) were used to identify the feasibility of the candidate CpG sites as biomarkers for asthma. Results: Compared with HCs, there was a differential mRNA expression for nine aging-related genes in peripheral blood of asthma patients. Besides, the methylation levels of the nine aging-related genes were also altered in asthma patients, and a total of 68 CpG sites were associated with the severity of asthma. Notably, 9 of the 68 CpG sites were significantly associated with pulmonary function parameters. Moreover, ROC curve and PCA analysis showed that the candidate differential methylation sites (DMSs) can be used as potential biomarkers for asthma. Conclusions: In summary, this study confirmed the differentially expressed mRNA and aberrant DNAm level of aging-related genes in asthma patients. DMSs are associated with the clinical evaluation indicators of asthma, which indicate the involvement of aging-related genes in the pathogenesis of asthma and provide some new possible biomarkers for asthma.

Keywords: DNA methylation; aging; aging-related genes; allergy; asthma.