DNA methylation of skeletal muscle function‐related secretary factors identifies FGF2 as a potential biomarker for sarcopenia

Autor: Jia‐Wen Li, Zheng‐Kai Shen, Yu‐Shuang Lin, Zhi‐Yue Wang, Mei‐Lin Li, Hui‐Xian Sun, Quan Wang, Can Zhao, Jin‐Shui Xu, Xiang Lu, Wei Gao
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Journal of Cachexia, Sarcopenia and Muscle, Vol 15, Iss 3, Pp 1209-1217 (2024)
Druh dokumentu: article
ISSN: 2190-6009
2190-5991
DOI: 10.1002/jcsm.13472
Popis: Abstract Background Sarcopenia is characterized by progressive loss of muscle mass and function due to aging. DNA methylation has been identified to play important roles in the dysfunction of skeletal muscle. The aim of our present study was to explore the whole blood sample‐based methylation changes of skeletal muscle function‐related factors in patients with sarcopenia. Methods The overall DNA methylation levels were analysed by using MethlTarget™ DNA Methylation Analysis platform in a discovery set consistent of 50 sarcopenic older adults (aged ≥65 years) and 50 age‐ and sex‐matched non‐sarcopenic individuals. The candidate differentially methylated regions (DMRs) were further validated by Methylation‐specific PCR (MSP) in another two independent larger sets and confirmed by pyrosequencing. Receiver operating characteristic (ROC) curve analysis was used to determine the optimum cut‐off levels of fibroblast growth factor 2 (FGF2)_30 methylation best predicting sarcopenia and area under the ROC curve (AUC) was measured. The correlation between candidate DMRs and the risk of sarcopenia was investigated by univariate analysis and multivariate logistic regression analysis. Results Among 1149 cytosine‐phosphate‐guanine (CpG) sites of 27 skeletal muscle function‐related secretary factors, 17 differentially methylated CpG sites and 7 differentially methylated regions (DMRs) were detected between patients with sarcopenia and control subjects in the discovery set. Further methylation‐specific PCR identified that methylation of fibroblast growth factor 2 (FGF2)_30 was lower in patients with sarcopenia and the level was decreased as the severity of sarcopenia increased, which was confirmed by pyrosequencing. Correlation analysis demonstrated that the methylation level of FGF2_30 was positively correlated to ASMI (r = 0.372, P
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