Effect of summer daylight exposure and genetic background on growth in growth hormone-deficient children

C De Leonibus; P Chatelain; C Knight; P Clayton; A Stevens

doi:10.1038/tpj.2015.67

Effect of summer daylight exposure and genetic background on growth in growth hormone-deficient children

Pharmacogenomics J. 2016 Nov;16(6):540-550. doi: 10.1038/tpj.2015.67. Epub 2015 Oct 27.

Authors

C De Leonibus¹, P Chatelain², C Knight³, P Clayton¹, A Stevens¹

Affiliations

¹ Institute of Human Development, University of Manchester and Royal Manchester Children's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.
² Department Pédiatrie, Hôpital Mère-Enfant-Université Claude Bernard, Lyon, France.
³ University of Manchester, Manchester, UK.

Abstract

The response to growth hormone in humans is dependent on phenotypic, genetic and environmental factors. The present study in children with growth hormone deficiency (GHD) collected worldwide characterised gene-environment interactions on growth response to recombinant human growth hormone (r-hGH). Growth responses in children are linked to latitude, and we found that a correlate of latitude, summer daylight exposure (SDE), was a key environmental factor related to growth response to r-hGH. In turn growth response was determined by an interaction between both SDE and genes known to affect growth response to r-hGH. In addition, analysis of associated networks of gene expression implicated a role for circadian clock pathways and specifically the developmental transcription factor NANOG. This work provides the first observation of gene-environment interactions in children treated with r-hGH.

Trial registration: ClinicalTrials.gov NCT00699855.

Publication types

Comparative Study
Multicenter Study
Research Support, Non-U.S. Gov't

MeSH terms

Body Height* / drug effects
Body Height* / genetics
Child
Child, Preschool
Female
Gene Regulatory Networks
Gene-Environment Interaction*
Genetic Background*
Genetic Predisposition to Disease
Growth Disorders / blood
Growth Disorders / drug therapy*
Growth Disorders / genetics*
Growth Disorders / physiopathology
Human Growth Hormone / blood
Human Growth Hormone / deficiency
Human Growth Hormone / therapeutic use*
Humans
Male
Nanog Homeobox Protein / genetics
Phenotype
Polymorphism, Single Nucleotide*
Prospective Studies
Recombinant Proteins / therapeutic use
Seasons*
Sunlight*
Time Factors
Treatment Outcome

Substances

NANOG protein, human
Nanog Homeobox Protein
Recombinant Proteins
Human Growth Hormone

Associated data

ClinicalTrials.gov/NCT00699855