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ABSTRACT:
Methods: The mRNA expression and DNA methylation of FOXO3 and TP53 in peripheral blood of 43 LOA patients (15 mild LOA, 15 moderate LOA and 13 severe LOA) and 60 healthy controls (HCs) were determined. The association of methylated sites with age was assessed by Cox regression to control the potential confounders. Then, the correlation between differentially methylated sites (DMSs; p-value?
Results: Compared with HCs, the mRNA expression and DNA methylation of FOXO3 and TP53 vary significantly in LOA patients. Besides, 8 DMSs from LOA patients were identified. Two of the DMSs, chr6:108882977 (FOXO3) and chr17:7591672 (TP53), were associated with the severity of LOA. The combination of the two DMSs and age could predict LOA with high accuracy (AUC values?=?0.924). In HDM-stressed asthma model, DNA demethylation increased the expression of FOXO3 and P53.
Conclusions: The mRNA expression of FOXO3 and TP53 varies significantly in peripheral blood of LOA patients, which may be due to the regulation of DNA methylation. FOXO3 and TP53 methylation is a suitable blood biomarker to predict LOA, which may be useful targets for the risk diagnosis and clinical management of LOA.
SUBMITTER: Yuan L
PROVIDER: S-EPMC7726856 | biostudies-literature | 2020 Dec
REPOSITORIES: biostudies-literature
Yuan Lin L Wang Leyuan L Du Xizi X Qin Ling L Yang Ming M Zhou Kai K Wu Mengping M Yang Yu Y Zheng Zhiyuan Z Xiang Yang Y Qu Xiangping X Liu Huijun H Qin Xiaoqun X Liu Chi C
Journal of translational medicine 20201209 1
<h4>Background</h4>Late-onset asthma (LOA) is beginning to account for an increasing proportion of asthma patients, which is often underdiagnosed in the elderly. Studies on the possible relations between aging-related genes and LOA contribute to the diagnosis and treatment of LOA. Forkhead Box O3 (FOXO3) and TP53 are two classic aging-related genes. DNA methylation varies greatly with age which may play an important role in the pathogenesis of LOA. We supposed that the differentially methylated ...[more]