A pilot study to evaluate gene expression profiles in peripheral blood mononuclear cells (PBMCs) from children with GH deficiency and Turner syndrome in response to GH treatment

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    Abstract

    Response to GH treatment is variable and dependent on diagnosis and dose. We used a pharmacogenomic approach to assess whether this variability is reflected in patterns of GH-induced gene expression in peripheral blood mononuclear cells (PBMCs) taken from three children with GH deficiency (GHD) and three girls with Turner syndrome (TS). Analysis of the response to GH treatment revealed that in GHD, 15 probe sets (11 genes) showed a fold change > +/- 1.4 at a P-value < 0.0005 (and a false detection rate <or= 15%). These genes included a suppressor of cytokine signalling (SOCS1) and a modulator of cAMP response elements (CREM). In marked contrast, in TS no genes fulfilled these criteria. ANOVA identified a subset of genes significantly affected by diagnosis, GH treatment or an interaction between diagnosis and treatment (P < 0.05, n = 2266). Cluster analysis indicated that genes up-regulated in both GHD and TS were related to DNA metabolism and transcription. Genes up-regulated in GHD but down-regulated in TS were involved in RNA processing and metabolism, whereas those down-regulated in GHD and up-regulated in TS were related to immune function. This pilot study has shown that major changes in gene expression in PBMCs can only be seen with confidence in GHD inferring that the pattern of gene expression in response to GH in GHD vs. TS is distinct and disease-specific. Further studies in larger cohorts will be required to evaluate whether GH-induced PBMCs gene expression patterns can predict responses to GH in a clinical setting.

    Original languageEnglish
    Pages (from-to)429-434
    Number of pages6
    JournalClinical Endocrinology
    Volume70
    Issue number3
    DOIs
    Publication statusPublished - Mar 2009

    Keywords

    • Child
    • Child, Preschool
    • Cluster Analysis
    • Computational Biology
    • Cyclic AMP Response Element Modulator/genetics
    • DNA/genetics
    • Female
    • Gene Expression Profiling
    • Growth Disorders/drug therapy
    • Growth Hormone/deficiency
    • Humans
    • Leukocytes, Mononuclear/metabolism
    • Male
    • Pilot Projects
    • RNA/genetics
    • Suppressor of Cytokine Signaling 1 Protein
    • Suppressor of Cytokine Signaling Proteins/genetics
    • Turner Syndrome/drug therapy

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