Ouni M, Castell A-L, Linglart As, Bougneres P. Genetic and epigenetic modulation of growth hormone sensitivity studied with the IGF1 generation test. The Journal of Clinical Endocrinology & Metabolism. http://press.endocrine.org/doi/abs/10.1210/jc.2015-1413
Context: Like all hormones, growth hormone (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 located within the proximal part of the P2 promoter of the insulin-like growth factor 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 IGF1 to a GH injection (IGF1 generation test) in a sample of 72 children with idiopathic short stature.
Results: While the d3 polymorphism of the GHR contributed 19% to the variance of the IGF1 response, CG-137 methylation in the IGF1 promoter contributed 30%, the combined contribution of the two factors totaling 43%.
Our observation indicates that genetic and epigenetic variation at the GHR and IGF1 loci play a major role as independent modulators of individual GH sensitivity.
Context: Like all hormones, growth hormone (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 located within the proximal part of the P2 promoter of the insulin-like growth factor 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 IGF1 to a GH injection (IGF1 generation test) in a sample of 72 children with idiopathic short stature.
Results: While the d3 polymorphism of the GHR contributed 19% to the variance of the IGF1 response, CG-137 methylation in the IGF1 promoter contributed 30%, the combined contribution of the two factors totaling 43%.
Our observation indicates that genetic and epigenetic variation at the GHR and IGF1 loci play a major role as independent modulators of individual GH sensitivity.
