A pharmacogenomic approach to the treatment of children with GH deficiency or Turner syndrome

Eur J Endocrinol. 2013 Jul 29;169(3):277-89. doi: 10.1530/EJE-13-0069. Print 2013 Sep.


Objective: Individual sensitivity to recombinant human GH (r-hGH) is variable. Identification of genetic factors contributing to this variability has potential use for individualization of treatment. The objective of this study was to identify genetic markers and gene expression profiles associated with growth response on r-hGH therapy in treatment-naïve, prepubertal children with GH deficiency (GHD) or Turner syndrome (TS).

Design: A prospective, multicenter, international, open-label pharmacogenomic study.

Methods: The associations of genotypes in 103 growth- and metabolism-related genes and baseline gene expression profiles with growth response to r-hGH (cm/year) over the first year were evaluated. Genotype associations were assessed with growth response as a continuous variable and as a categorical variable divided into quartiles.

Results: Eleven genes in GHD and ten in TS, with two overlapping between conditions, were significantly associated with growth response either as a continuous variable (seven in GHD, two in TS) or as a categorical variable (four more in GHD, eight more in TS). For example, in GHD, GRB10 was associated with high response (≥ Q3; P=0.0012), while SOS2 was associated with low response (≤ Q1; P=0.006), while in TS, LHX4 was associated with high response (P=0.0003) and PTPN1 with low response (P=0.0037). Differences in expression were identified for one of the growth response-associated genes in GHD (AKT1) and for two in TS (KRAS and MYOD1).

Conclusions: Carriage of specific growth-related genetic markers is associated with growth response in GHD and TS. These findings indicate that pharmacogenomics could have a role in individualized management of childhood growth disorders.

Trial registration: ClinicalTrials.gov NCT00699855.

Publication types

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

MeSH terms

  • Body Height / drug effects
  • Child
  • Child Development / drug effects
  • Drug Resistance
  • Female
  • Follow-Up Studies
  • GRB10 Adaptor Protein / genetics
  • GRB10 Adaptor Protein / metabolism
  • Genome-Wide Association Study
  • Growth Disorders / etiology
  • Growth Disorders / prevention & control
  • Hormone Replacement Therapy
  • Human Growth Hormone / deficiency*
  • Human Growth Hormone / therapeutic use*
  • Humans
  • LIM-Homeodomain Proteins / genetics
  • LIM-Homeodomain Proteins / metabolism
  • Male
  • Polymorphism, Single Nucleotide*
  • Prospective Studies
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1 / genetics*
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1 / metabolism
  • Recombinant Proteins / therapeutic use
  • Son of Sevenless Proteins / genetics*
  • Son of Sevenless Proteins / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Turner Syndrome / blood
  • Turner Syndrome / drug therapy*
  • Turner Syndrome / genetics*
  • Turner Syndrome / metabolism


  • GRB10 protein, human
  • LHX4 protein, human
  • LIM-Homeodomain Proteins
  • Recombinant Proteins
  • SOS2 protein, human
  • Son of Sevenless Proteins
  • Transcription Factors
  • Human Growth Hormone
  • GRB10 Adaptor Protein
  • PTPN1 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1

Associated data

  • ClinicalTrials.gov/NCT00699855