Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2008) 16 P371

ECE2008 Poster Presentations Growth factors (15 abstracts)

The cytosine-adenine (CA) repeat polymorphism in the promoter region of the insulin-like growth factor-1 (IGF-1) gene is not associated with the GH dose in GH-deficient adults

Silke Meyer 1 , Carolin Brück 1 , Diana Ivan 1 , Ute Köhler 1 , Stephan Schäfer 1 , Pascal Arp 3 , Aart J van der Lely 2 , Andre G Uitterlinden 3 & Peter H Kann 1

1Division of Endocrinology and Diabetology, University Hospital Giessen and Marburg GmbH, Philipps-University Marburg, Marburg, Germany; 2Department of Internal Medicine, Erasmus University Medical School, Rotterdam, The Netherlands; 3Department of Epidemiology and Biostatistics, Erasmus University Medical School, Rotterdam, The Netherlands.

Objective: A cytosine-adenine (CA)n microsatellite repeat polymorphism in the promoter region of the insulin-like growth factor-1 (IGF-1) gene has reported to be associated with IGF-1 serum levels, birth weight, body height, bone mineral density and risk for type 2 diabetes and myocardial infarction. Carriers and non-carriers of the most frequent allele (length 192 base pairs (bp)) showed significantly different total IGF-1 serum levels. This polymorphism may directly or indirectly influence growth hormone (GH)-mediated regulation of IGF-1 secretion.

Aim of this study was to test the hypothesis that the 192 bp polymorphism is associated with the GH dose of GH-deficient adult patients receiving recombinant GH-treatment.

Patients and methods: The 192 bp polymorphism was determined in 133 German adult patients (66 men, 67 women; mean age 45.4 years±13.1 S.D.; majority Caucasian) with GH-deficiency (GHD) of different origin, derived from the prospective KIMS Pharmacogenetics Study (approval was obtained from the local ethical committee). Patients received GH-treatment for 12 months with finished dose-titration of GH and standardized IGF-1 measurements. GH dose after one year of treatment, IGF- and IGF-SDS values and anthropometric data were analyzed by 192 bp polymorphism genotypes (homozygotes for the 192 bp allele; heterozygotes; non-carriers).

Results: The genotype distribution followed Hardy-Weinberg-equilibrium (P=0.06). Genotype groups showed no significant differences in the required GH dose after 1 year of GH-treatment (P=0.61), IGF-1 serum concentrations (P=0.78) and IGF-1 SDS (P=0.93) after adjusting for the confounding variables gender, age and body mass index.

Conclusion: The 192 bp polymorphism was not associated with the responsiveness to exogenous GH in GHD adults. As effects of non-GH factors on the IGF-1 levels (insulin-levels, sex steroids, nutrition, liver function) in GH-deficient patients were minimized, GH-driven regulation of IGF-1 levels seems not to be influenced by the 192 bp polymorphism in these patients.

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