Document Type
Article
Publication Date
5-18-2022
Identifier
DOI: 10.1186/s13148-022-01281-z; PMCID: PMC9118695
Abstract
BACKGROUND: Recombinant human growth hormone (rhGH) has shown a great growth-promoting potential in children with idiopathic short stature (ISS). However, the response to rhGH differs across individuals, largely due to genetic and epigenetic heterogeneity. Since epigenetic marks on the methylome can be dynamically influenced by GH, we performed a comprehensive pharmacoepigenomics analysis of DNA methylation changes associated with long-term rhGH administration in children with ISS.
RESULTS: We measured DNA methylation profiles before and after GH treatment (with a duration of ~ 18 months in average) on 47 healthy children using customized methylC-seq capture sequencing. Their changes were compared and associated with changes in plasma IGF1 by adjusting sex, age, treatment duration and estimated blood proportions. We observed a considerable inter-individual heterogeneity of DNA methylation changes responding to GH treatment. We identified 267 response-associated differentially methylated cytosines (DMCs) that were enriched in promoter regions, CpG islands and blood cell-type-specific regulatory elements. Furthermore, the genes associated with these DMCs were enriched in the biology process of "cell development," "neuron differentiation" and "developmental growth," and in the TGF-beta signaling pathway, PPAR Alpha pathway, endoderm differentiation pathway, adipocytokine signaling pathway as well as PI3K-Akt signaling pathway, and cAMP signaling pathway.
CONCLUSION: Our study provides a first insight in DNA methylation changes associated with rhGH administration, which may help understand mechanisms of epigenetic regulation on GH-responsive genes.
Journal Title
Clin Epigenetics
Volume
14
Issue
1
First Page
65
Last Page
65
MeSH Keywords
Child; CpG Islands; DNA Methylation; Epigenesis, Genetic; Human Growth Hormone; Humans; Phosphatidylinositol 3-Kinases; Recombinant Proteins
Keywords
DNA methylation; Growth hormone; Idiopathic short stature; Intervention epigenetics; Pharmacoepigenomics
Recommended Citation
Shao X, Le Stunff C, Cheung W, et al. Differentially methylated CpGs in response to growth hormone administration in children with idiopathic short stature. Clin Epigenetics. 2022;14(1):65. Published 2022 May 18. doi:10.1186/s13148-022-01281-z
Comments
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Publisher's Link: https://clinicalepigeneticsjournal.biomedcentral.com/articles/10.1186/s13148-022-01281-z