Pharmacogenomics of insulin-like growth factor-I generation during GH treatment in children with GH deficiency or Turner syndrome

Pharmacogenomics J. 2014 Feb;14(1):54-62. doi: 10.1038/tpj.2013.14. Epub 2013 Apr 9.


Individual responses to growth hormone (GH) treatment are variable. Short-term generation of insulin-like growth factor-I (IGF-I) is recognized as a potential marker of sensitivity to GH treatment. This prospective, phase IV study used an integrated genomic analysis to identify markers associated with 1-month change in IGF-I (ΔIGF-I) following initiation of recombinant human (r-h)GH therapy in treatment-naïve children with GH deficiency (GHD) (n=166) or Turner syndrome (TS) (n=147). In both GHD and TS, polymorphisms in the cell-cycle regulator CDK4 were associated with 1-month ΔIGF-I (P<0.05). Baseline gene expression was also correlated with 1-month ΔIGF-I in both GHD and TS (r=0.3; P<0.01). In patients with low IGF-I responses, carriage of specific CDK4 alleles was associated with MAPK and glucocorticoid receptor signaling in GHD, and with p53 and Wnt signaling pathways in TS. Understanding the relationship between genomic markers and early changes in IGF-I may allow development of strategies to rapidly individualize r-hGH dose.

Publication types

  • Clinical Trial, Phase IV
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Child
  • Child, Preschool
  • Cyclin-Dependent Kinase 4 / genetics
  • Female
  • Gene Expression Profiling
  • Growth Disorders / blood
  • Growth Disorders / drug therapy*
  • Growth Disorders / genetics
  • Hormone Replacement Therapy
  • Human Growth Hormone / deficiency*
  • Human Growth Hormone / therapeutic use*
  • Humans
  • Infant
  • Insulin-Like Growth Factor I / analysis*
  • Male
  • Polymorphism, Single Nucleotide*
  • Prospective Studies
  • Recombinant Proteins
  • Transcriptome
  • Turner Syndrome / blood
  • Turner Syndrome / drug therapy*
  • Turner Syndrome / genetics


  • Recombinant Proteins
  • Human Growth Hormone
  • Insulin-Like Growth Factor I
  • CDK4 protein, human
  • Cyclin-Dependent Kinase 4