Searchable abstracts of presentations at key conferences in endocrinology

ea0028oc5.2 | Growth, tumours and pituitary | SFEBES2012

A network analysis of gene expression through childhood highlights changes related to age and growth

Stevens Adam , Whatmore Andrew , Clayton Peter

Objective: To assess age- and growth-dependent gene expression in children and correlate this with biological pathways.Methods: We conducted a gene expression meta-analysis on datasets from normal children curated from the NCBI Gene Expression Omnibus (GEO). Four datasets were combined to form a group of 87 individuals ranging from 0.2 to 29.3 years of age (average 7.7±6.9yr). Analysis of gene expression data was performed using hierarchical cluster...

ea0085p83 | Pituitary and Growth 2 | BSPED2022

DNA haplotypes influencing the response to growth hormone therapy are disproportionately inherited from neanderthals

Murray Philip , Hussain Asad , Garner Terence , Stevens Adam

Background: Neanderthals split from an ancestral human population ~500,000 years ago and lived in Eurasia until 40,000 years ago. Early modern humans emerged in Africa ~350,000 years ago migrating into Eurasia 50,000 years ago. Interbreeding occurred between early modern humans and Neanderthals leading to the introduction of Neanderthal DNA into the early human population, a process termed introgression. In modern Eurasian populations around 2-4% of DNA is of Neanderthal origi...

ea0058oc4.2 | Oral Communications 4 | BSPED2018

Gene expression signatures in children with growth hormone deficiency (GHD) and Turner syndrome (TS) predict response to growth hormone

Clayton Peter , Stevens Adam , Murray Philip , Garner Terence

Background: Recombinant human growth hormone (r-hGH) is the primary therapeutic agent for disorders of growth including growth hormone deficiency (GHD) and Turner syndrome (TS). There is a high cost associated with treatment and existing methods to predict response (and hence alter management) can only account for 40–60% of the variance.Methods: GHD (n=71) and TS patients (n=43) were recruited as part of a study (PREDICT) on the lo...

ea0034p164 | Growth and development | SFEBES2014

Distinct gene expression is associated with epigenetic and growth-related network modules in relation to gender differences in the timing of the pubertal growth spurt

De Leonibus Chiara , Chatelain Pierre , Clayton Peter , Stevens Adam

Background: The return to active long bone growth in puberty is a distinctly human event1 and occurs ~2 years earlier in girls compared to boys. Evolutionarily conserved networks of genes are associated with the developmental phases of childhood in multiple tissues2, implying the existence of a genetic program that controls the pubertal return to growth.Objectives: To identify biological functions associated with gender and age-rela...

ea0033p67 | (1) | BSPED2013

Effect of latitude, summer daylight exposure and genetic background on growth response to recombinant human GH in GH deficient patients

De Leonibus Chiara , Chatelain Pierre , Clayton Peter , Stevens Adam

Introduction: Growth rate tends to be greater in children living at higher latitudes although the underlying mechanisms are unclear. The aim of this study was to compare height velocity (HV) in response to recombinant human GH (r-hGH) therapy in children with GH deficiency (GHD) living at different latitudes.Design: Pre-pubertal children with GHD (n=118) were enrolled from the PREDICT long-term follow-up prospective study (NCT00699855). Data wer...

ea0025p205 | Growth and development | SFEBES2011

Identification of turner syndrome specific mRNA expression profiles that correlate with clinical response to growth hormone

Stevens Adam , Tajbakhsh Shahin , Whatmore Andrew , Westwood Melissa , Clayton Peter

Girls with Turner syndrome (TS) are treated with recombinant human growth hormone (rhGH) to improve their adult height but the gain is variable (0–20 cm). Current prediction models can account for only ~46% of the variability in the first year response to rhGH, thus genetic profiling has been suggested as a possible means of improving this prediction. The aim of this study was to explore mRNA expression profiles in an ex-vivo fibroblast model to characterise response to r...

ea0085oc5.4 | Oral Communications 5 | BSPED2022

Greater postnatal adiposity gain following inadequate fetal growth in the manchester babyGRO study

Perchard Reena , Higgins Lucy , Stevens Adam , Whatmore Andrew , Johnstone Edward , Clayton Peter

Background: Previous studies use small for gestational age (SGA) as a surrogate marker for fetal growth restriction (FGR). SGA individuals, particularly those who show catch-up growth have greater cardiometabolic (CM) risk than those born appropriate for gestational age. However, not all FGR fetuses are born SGA. Therefore, we studied neonates born following pregnancies at increased risk of FGR, irrespective of birthweight.Aim: To define associations bet...

ea0085oc6.2 | Oral Communications 6 | BSPED2022

The Arginine-nitric-oxide pathway links suboptimal fetal growth to higher childhood systolic blood pressure in the manchester babyGRO study

Perchard Reena , Higgins Lucy , Stevens Adam , Garner Terence , Whatmore Andrew , Johnstone Edward , Clayton Peter

Background: Cardiometabolic (CM) risk is linked to being small for gestational age (SGA, birthweight <-2SDS). Suboptimal fetal growth alone may be linked with greater CM risk without resulting in SGA. Therefore, we focused on CM risk in children born following pregnancies at higher risk for growth restriction, irrespective of birthweight.Aims: 1. To identify associations between fetal and childhood weight trajectories and CM risk markers. 2. To defin...

ea0036oc3.7 | Oral Communications 3 | BSPED2014

Patterns of gene expression in pre-pubertal children are associated with the severity of their GH deficiency

Stevens Adam , De Leonibus Chiara , Chatelain Pierre , Murray Philip , Clayton Peter

Background: GH deficiency (GHD) has a spectrum of severity as characterised by GH stimulation tests; the cut-off level for GHD has been a long standing contentious issue. An independent biological correlate of severity would be valuable.Objectives: To identify patterns of gene expression (GE) that correlate with severity in GHD.Methods: Pre-pubertal children with GHD (n=72) were enrolled from the PREDICT study (NCT00256126...

ea0031oc4.3 | Obesity, metabolism and bone | SFEBES2013

Adult offspring of undernourished sheep exhibit epigenetic alterations in HPA axis glucocorticoid receptor

Begum Ghazala , Stevens Adam , Oliver Mark , Jaquiery Anne , Harding Jane , Challis John , Bloomfield Frank , White Anne

Maternal programming increases the risk of alterations in the offspring’s HPA axis. Previously we showed that maternal undernutrition in sheep induces epigenetic changes in the glucocorticoid receptors (GR) within hypothalamic energy balance pathways, without affecting HPA axis GR. However, these studies focussed on fetal tissues1. Here, we investigated whether GR is epigenetically altered in the HPA axis of adult offspring to determine the status of the pathwa...