Endocrine Abstracts (2013) 32 P625 | DOI: 10.1530/endoabs.32.P625

SNPs within the GH signaling pathway are associated with the fast, but not the long term, IGF1 response to GH replacement therapy in GH deficient adults

Camilla Glad1,2, Edna de Jesus Litenski Barbosa3, Helena Filipsson Nyström1, Lena Carlsson Ekander2, Staffan Nilsson4, Anna Nilsson1, Per-Arne Svensson2 & Gudmundur Johannsson1


1Department of Endocrinology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; 2Department of Molecular and Clinical Medicine, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; 3Serviço de Endocrinologia e Metabologia do Hospital de Clínicas da Universidade Federal do Paraná, Curitiba, Brazil; 4Department of Mathematical Statistics, Chalmers University of Technology, Gothenburg, Sweden.


Introduction: GH deficiency (GHD) in adults is associated with low serum levels of insulin-like growth factor 1 (IGF1) and a deteriorated cardio-metabolic profile. GH replacement therapy (GHRT) increases serum IGF1, an important mediator of the treatment response and safety marker of dose titration. The interindividual variation in treatment response is large and most likely influenced by genetic factors.

Aim: The aim of this study was to test the hypothesis that single-nucleotide polymorphisms (SNPs) in genes within the GH signaling pathway impact on the fast (1 week) and/or long term (6 months and 1 year) IGF1 response to GHRT.

Patients and methods: Three hundred and thirteen consecutive GHD subjects (58.1% men; mean age 49.7 years) were studied before and after 1 week, 6 months and 1 year of GHRT. Response was defined as the percentage of change in IGF1 levels from baseline (fast response) and from 1 week (long term response). Six SNPs in the GHR, JAK2, STAT5b, SOCS2 and PIK3CB genes were selected for genotyping.

Results: Average genotyping success rate was 98.8%. In linear regression analyses adjusting for sex, age and the GH dose, SNPs rs6873545 (GHR) and rs361072 (PIK3CB) were significantly associated with the percentage of change in IGF1 levels at 1 week of GHRT (P=0.031 and P=0.017 respectively). No SNP was significantly associated with the long term response.

Conclusion: Our results indicate that common genetic variants in genes with function in the GH signaling pathway may be of functional relevance to the fast response to GHRT in GHD adults. In addition, these results highlight the fact that genetic factors are more likely to impact on the fast response to RT, when factors such as individual dose titrations, diet and life style choices etc. are less likely to influence the response marker.