ESPE Abstracts

Background: The diagnosis of Growth Hormone Deficiency (GHD) involves the use of GH stimulation tests that require day case admission, multiple blood sampling and are associated with significant adverse effects.Aim: To assess the utility of gene expression (GE) profiling and candidate SNP analysis for the diagnosis of and classification of GHD.Method: Pre-pubertal treatment-naïve children with GHD (n=98) were enrolled from the...

Background: Single nucleotide polymorphisms (SNPs) within the promotor and 5’UTR of the transcriptional factor, ZBTB38, are associated with adult height and idiopathic short stature although their precise auxological effects have not previously been described. In addition, the molecular mechanisms through which ZBTB38 affects growth have not been fully elucidated but potential downstream mediators are suggested to include MCM10 or IGF2.Objectives: <...

Background: The relationship of pre-treatment gene expression (GE) to long-term growth response in GHD is unknown. Prediction of long-term response to r-hGH therapy would allow better decision making about start and maintenance doses and hence cost:benefit.Objective and hypotheses: To assess the relationship of baseline GE to response to r-hGH over 5 years of therapy in GHD children.Method: Pre-pubertal children with GHD (n</em...

Introduction: Growth promoting effects of GH occur in parallel with its impact on insulin sensitivity and lipid metabolism; underlying biological networks that link these actions are not defined. Our objective was to identify gene expression (GE) networks linking growth with metabolic responses in GH-treated children with GHD.Methods/design: Pre-pubertal children with GH Deficiency GHD (n=125) were enrolled from the PREDICT short-term (NCT002561...

Growth response to daily GH treatment can be predicted using pre-treatment gene expression profiles.1 Once-weekly GH treatment potentially reduces the burden of daily injections2 and thus may be a major advancement in care for patients with GHD, vs standard, daily GH treatment. Here we investigate the prediction of first-year growth response based on pre-treatment blood transcriptome in children with GHD undergoing treatment with daily or once-weekly GH. ...

Background: Cardiometabolic (CM) risk is linked to being small for gestational age (SGA, birthweight <-2SDS). Fetal growth restriction (FGR) may not result in SGA. We focused on potential CM risk in children born following pregnancies at higher risk for FGR.Aims: To identify associations between fetal and childhood weight trajectory quartiles and CM risk markers. 2.To define molecular pathways potentially associated w...

Background: Children born SGA are known to develop cardiometabolic conditions in adulthood1. Nothing is known about the relationship of the transcriptome (gene expression) and epigenome (DNA methylation) to birth size and the future development of cardiometabolic disease.Aim: To identify, I) differences and functional links between epigenome age-7years, transcriptome age-9years associated and ...

Background: Current data from genome wide association studies (GWAS) explains 24.6% of the variation in adult height from 3290 single nucleotide polymorphisms (SNPs)1. Data on the genetic control of growth velocity during childhood is more limited and no previous studies have linked childhood growth to changes in the transcriptome (gene expression) or epigenome (DNA methylation). Here we present a systems biology approach to understand mid-child...

Background: GRB10 negatively regulates IGF1 signalling, influences growth and promoter polymorphisms are associated with GH response1. GRB10 knockout-mouse models display foetal overgrowth2, however, the mouse model has only partial similarity to human growth3. There is evidence that the zebrafish is an appropriate model to study growth4 and has the advantage of being easily genetically manipulated.<p class="abs...

Background: The phases of human growth are associated with gene expression (GE) changes1, raising the possibility that rhythmic patterns of GE occur throughout childhood.Objective: In this study, we have assessed time-series patterns of GE profiles associated with age to characterise oscillations.Methods: GE analysis was conducted on cells of lymphoid origin from normal individuals through childhood (n=87, 43 ma...