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Differentially methylated CpGs in response to growth hormone administration in children with idiopathic short stature

From National Research Council Canada

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DOIResolve DOI: https://doi.org/10.1186/s13148-022-01281-z
AuthorSearch for: 1ORCID identifier: https://orcid.org/0000-0002-3044-621X; Search for: ; Search for: ; Search for: ; Search for: ; Search for: ; Search for:
Affiliation
  1. National Research Council Canada. Digital Technologies
FunderSearch for: Canadian Institutes of Health Research; Search for: Agence Nationale de la Recherche
FormatText, Article
Physical description12 p.
Subjectpharmacoepigenomics; growth hormone; DNA methylation; intervention epigenetics; idiopathic short stature
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.
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PublisherBMC
Springer Nature
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  • Clinical Epigenetics 14, no. 1, 65 (December 2022).
LanguageEnglish
Peer reviewedYes
Identifier1281
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Record identifier7be8496c-ce81-435f-9b6b-28fe9dfdf3b5
Record created2022-07-14
Record modified2023-01-25
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