Endocrine Abstracts (2010) 24 OC1.4

The Growth Hormone Receptor Exon 3 Deleted Polymorphism is Associated with Birth and Placental Weight

R Padidela1, S Bryan1, S Abu-Amero2, R Hudson-Davies1, J Achermann1, G Moore1 & P Hindmarsh1


1Developmental Endocrinology Research Group, Institute of Child Health, University College London, London, UK; 2Clinical & Molecular Genetics Unit, Institute of Child Health, University College London, London, UK.


In humans Growth Hormone Receptor (GHR) transcripts exist in two isoforms, the full-length (GHRfl) or exon 3 deletion isoform (GHRd3). Individuals with the GHRd3 isoform are associated with an increased response to recombinant human GH. The d3/fl-GHR polymorphism does not influence adult height. However, an association with the d3/fl-GHR polymorphism has been found with antenatal growth especially in small for gestational age (SGA) infants. Here we demonstrate that the d3/fl-GHR polymorphism influences both birth and placental weight in white Caucasians (n=1048) derived from the University College London Hospital Fetal Growth Study (UCL-FGS) and Moore-Well-being of Women Baby-Bio-Bank cohort.

Study Methods: Uncomplicated singleton white Caucasian pregnancies were recruited by the UCL-FGS (n=1650) and the Baby Bio Bank cohort (n=310). Genomic DNA was available for analysis from 774 infants from the UCL-FGS and 274 from the Baby Bio Bank cohort. The two isoforms GHR transcript variants were analysed using multiplex PCR.

Results: The frequency of d3/fl-GHR polymorphism was similar to previous reports and within the Hardy-Weinberg equilibrium. There were no demographic differences in birth weight and placental weight between the genotyped group and the total cohort mean. There was a significant underrepresentation of wild type fl/fl (29%) and overrepresentation of d3/d3 (14%) genotype in the SGA infants within the cohort (Chi square 17.7, P<0.001). Fl/fl was overrepresented in LGA infants (Chi square 5.79, P=0.05). ANOVA with post hoc test demonstrated a significant association of GHR isoforms with placental weight (P<0.001) and birth weight SDS (P=0.04) with the d3/d3 genotype associated with a smaller size. In stepwise regression analysis the d3/fl-GHR genotype, booking weight and parity influenced placental weight (R=0.35; P<0.001). This genotype was not related with antenatal anthropometric measurements, cord concentration of growth hormone or insulin like growth factor 1 & 2 or postnatal size.

Conclusion: These data suggest that the d3/fl-GHR genotype is associated with placental weight and birth weight.

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