title: The P2 promoter of the IGF1 gene is a major epigenetic locus for GH responsiveness.
abstract: Short children using growth hormone (GH) to accelerate their growth respond to this treatment with a variable efficacy. The causes of this individual variability are multifactorial and could involve epigenetics. Quantifying the impact of epigenetic variation on response to treatments is an emerging challenge. Here we show that methylation of a cluster of CGs located within the P2 promoter of the insulin-like growth factor 1 (IGF1) gene, notably CG-137, is inversely closely correlated with the response of growth and circulating IGF1 to GH administration. For example, variability in CG-137 methylation contributes 25% to variance of growth response to GH. Methylation of CGs in the P2 promoter is negatively associated with the increased transcriptional activity of P2 promoter in patients' mononuclear blood cells following GH administration. Our observation indicates that epigenetics is a major determinant of GH signaling (physiology) and of individual responsiveness to GH treatment (pharmacoepigenetics).
authors: Institut National de la Santé et de la Recherche Médicale U986, Paris Sud University, Bicêtre Hospital, Le Kremlin-Bicêtre, France.
authors: M
authors: M
authors: Ouni
authors: Institut National de la Santé et de la Recherche Médicale U986, Paris Sud University, Bicêtre Hospital, Le Kremlin-Bicêtre, France.
authors: M P
authors: MP
authors: Belot
authors: Department of Pediatric Endocrinology and Diabetes, Paris Sud University, Bicêtre Hospital, Le Kremlin-Bicêtre, France.
authors: A L
authors: AL
authors: Castell
authors: Institut National de la Santé et de la Recherche Médicale U986, Paris Sud University, Bicêtre Hospital, Le Kremlin-Bicêtre, France.
authors: D
authors: D
authors: Fradin
authors: Institut National de la Santé et de la Recherche Médicale U986, Paris Sud University, Bicêtre Hospital, Le Kremlin-Bicêtre, France.|Department of Pediatric Endocrinology and Diabetes, Paris Sud University, Bicêtre Hospital, Le Kremlin-Bicêtre, France.
authors: P
authors: P
authors: Bougnères
mesh_terms: D001773:Blood Cells / Q000378:metabolism; D002648:Child; D018899:CpG Islands; D019175:DNA Methylation; D004392:Dwarfism / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D044127:Epigenesis, Genetic; D005260:Female; D056426:Genetic Loci; D019382:Human Growth Hormone / Q000627:therapeutic use*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics* / Q000378:metabolism; D008297:Male; D011401:Promoter Regions, Genetic; D011994:Recombinant Proteins / Q000627:therapeutic use; D014158:Transcription, Genetic
chemical_list: C583557:IGF1 protein, human; D011994:Recombinant Proteins; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I