Effect of summer daylight exposure and genetic background on growth in growth hormone-deficient children.
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.
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.
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De Leonibus
Department Pédiatrie, Hôpital Mère-Enfant-Université Claude Bernard, Lyon, France.
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Chatelain
University of Manchester, Manchester, UK.
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Knight
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.
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Clayton
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.
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Stevens
D001827:Body Height / Q000187:drug effects / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D005260:Female; D053263:Gene Regulatory Networks; D059647:Gene-Environment Interaction; D000068617:Genetic Background; D020022:Genetic Predisposition to Disease; D006130:Growth Disorders / Q000097:blood / Q000188:drug therapy* / Q000235:genetics* / Q000503:physiopathology; D019382:Human Growth Hormone / Q000097:blood / Q000172:deficiency / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D000071317:Nanog Homeobox Protein / Q000235:genetics; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000627:therapeutic use; D012621:Seasons; D013472:Sunlight; D013997:Time Factors; D016896:Treatment Outcome
C486780:NANOG protein, human; D000071317:Nanog Homeobox Protein; D011994:Recombinant Proteins; D019382:Human Growth Hormone