title: Genetic and Epigenetic Modulation of Growth Hormone Sensitivity Studied With the IGF-1 Generation Test.
abstract: BACKGROUND
  Like all hormones, GH has variable physiological effects across people. Many of these effects initiated by the binding of GH to its receptor (GHR) in target tissues are mediated by the expression of the IGF1 gene. Genetic as well as epigenetic variation is known to contribute to the individual diversity of GH-dependent phenotypes through two mechanisms. The first one is the genetic polymorphism of the GHR gene due to the common deletion of exon 3. The second, more recently reported, is the epigenetic variation in the methylation of a cluster of CGs dinucleotides located within the proximal part of the P2 promoter of the IGF-1 (IGF1) gene, notably CG-137.
  
  
  OBJECTIVE
  The current study evaluates the relative contribution of these two factors controlling individual GH sensitivity by measuring the response of serum IGF-1 to a GH injection (IGF-1 generation test) in a sample of 72 children with idiopathic short stature.
  
  
  RESULTS
  Although the d3 polymorphism of the GHR contributed 19% to the variance of the IGF-1 response, CG-137 methylation in the IGF-1 promoter contributed 30%, the combined contribution of the two factors totaling 43%.
  
  
  CONCLUSIONS
  Our observation indicates that genetic and epigenetic variation at the GHR and IGF-1 loci play a major role as independent modulators of individual GH sensitivity.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale Unité 986 (M.O., A.-L.C., A.L., P.B.) and Department of Pediatric Endocrinology and Diabetes (A.-L.C., A.L., P.B.), Paris Sud University, Bicêtre Hospital, 94275 Le Kremlin-Bicêtre, France.
authors.forename: Meriem
authors.initials: M
authors.lastname: Ouni
authors.affiliation: Institut National de la Santé et de la Recherche Médicale Unité 986 (M.O., A.-L.C., A.L., P.B.) and Department of Pediatric Endocrinology and Diabetes (A.-L.C., A.L., P.B.), Paris Sud University, Bicêtre Hospital, 94275 Le Kremlin-Bicêtre, France.
authors.forename: Anne-Laure
authors.initials: AL
authors.lastname: Castell
authors.affiliation: Institut National de la Santé et de la Recherche Médicale Unité 986 (M.O., A.-L.C., A.L., P.B.) and Department of Pediatric Endocrinology and Diabetes (A.-L.C., A.L., P.B.), Paris Sud University, Bicêtre Hospital, 94275 Le Kremlin-Bicêtre, France.
authors.forename: Agnès
authors.initials: A
authors.lastname: Linglart
authors.affiliation: Institut National de la Santé et de la Recherche Médicale Unité 986 (M.O., A.-L.C., A.L., P.B.) and Department of Pediatric Endocrinology and Diabetes (A.-L.C., A.L., P.B.), Paris Sud University, Bicêtre Hospital, 94275 Le Kremlin-Bicêtre, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Bougnères
mesh_terms: D000293:Adolescent; D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D019175:DNA Methylation; D003940:Diagnostic Techniques, Endocrine; D004351:Drug Resistance / Q000235:genetics*; D044127:Epigenesis, Genetic / Q000502:physiology; D005260:Female; D005838:Genotype; D006130:Growth Disorders / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D019382:Human Growth Hormone / Q000627:therapeutic use*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism*; D008297:Male; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic
chemical_list: D002352:Carrier Proteins; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; C051815:somatotropin-binding protein
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