ESPE Abstracts (2015) 84 P-1-78

Influence of Genetic Variation on the Response to Recombinant Human Growth Hormone Treatment in Children with GH Deficiency: An Analysis of 13 Single Nucleotide Polymorphisms and the GH Receptor Exon 3 Deletion

Anna-Maria Junga, Paul Francois Hoffmanna, Dominik Monza, Christina Lissewskib, Denny Schanzeb, Martin Zenkerb & Tilman Robert Rohrera


aDepartment of Pediatrics and Adolescent Medicine, Division of Pediatric Endocrinology, Saarland University Medical Center, Homburg, Germany; bInstitute of Human Genetics, University Hospital Magdeburg, Magdeburg, Germany


Background: Growth hormone deficiency (GHD) is the most common endocrine cause of impaired growth. Recombinant human GH (rhGH) therapy does not always achieve complete catch-up growth or final height within the genetic target height despite standardised treatment guidelines. The factors causing the considerable variability in responsiveness to rhGH have not yet been fully elucidated. Apart from a number of auxological and clinical parameters, genetic factors also appear to play an important role.

Objective and hypotheses: We analysed 13 single nucleotide polymorphisms (SNPs) located in genes of the GH axis, the growth plate, and the cell cycle, as well as the exon 3 deletion of the GH receptor (GHR) to explore their potential influence on patients’ responsiveness to rhGH therapy.

Method: The study involved 101 children treated with rhGH for GHD. Thirteen SNPs were genotyped using high resolution melting analysis and sequencing. Furthermore the frequency of the growth hormone receptor exon 3 deletion was determined by PCR using a combination of different primers. The index of responsiveness (IoR) was used as an objective measure of response to rhGH therapy. IoR values were compared by genotype for each SNP using one-way ANOVA.

Results: For the rs2888586 SNP in the SOS1 gene, the TT genotype was associated with increased IoR values compared to CT and CC. For rs2069502 in the CDK4 gene, the G allele was associated with increased IoR values compared to the A allele. Furthermore, patients with the exon 3 deletion in the GHR gene had higher IoR values.

Conclusion: The results of our study indicate that genetic analyses are a starting point for the individualised treatment of GHD. Thus, the genetic variations investigated may serve as predictive markers of response to rhGH treatment in GHD.

Conflict of interest: T R Rohrer is a member of the Nordinet® IOS International study committee and has received consultation fees and speaker’s honoraria from Ferring, Novo Nordisk, MerckSerono and Pfizer. Research grants from MerckSerono, Novo Nordisk, and Pfizer.

Funding: This study was funded by an unrestricted grant from Pfizer WI172376.