Growth hormone dose in growth hormone-deficient adults is not associated with

• Published in: Pharmacogenomics Vol. 10; no. 2; pp. 293 - 302
• Main Authors: Meyer, Silke, Schaefer, Stephan, Ivan, Diana, Stolk, Lisette, Arp, Pascal, Uitterlinden, Andréé G, Nawroth, Peter P, Plööckinger, Ursula, Stalla, Güünter K, Tuschy, Ulrich, Weber, Matthias M, Weise, Alexander, Pfüützner, Andreas, Kann, Peter H
• Format: Journal Article
• Language: English
• Published: Future Medicine Ltd 01.02.2009
• Subjects: cytosine-–adenine (CA); GH-dose; GHD; growth hormone; growth hormone deficiency; IGF-1; repeat polymorphism; SNP; tagging SNP
• ISSN: 1462-2416; 1744-8042
• DOI: 10.2217/14622416.10.2.293

Several SNPs and a microsatellite cytosine-–adenine repeat promoter polymorphism of the gene have been reported to be associated with circulating IGF-1 serum concentrations. Variance in IGF-1 concentrations due to genetic variations may affect different response to growth hormone (GH) treatment, resulting in different individually required GH-doses in GH-deficient patients. The aim of this study was to test if the gene polymorphisms are associated with the GH-dose of GH-deficient adults. A total of nine tagging SNPs, five additionally selected SNPs and a cytosine-–adenine repeat polymorphism were determined in 133 German adult patients (66 men, 67 women; mean age 45.4 years ±± 13.1 standard deviation; majority Caucasian) with GH-deficiency (GHD) of different origin, derived from the prospective Pfizer International Metabolic Study (KIMS) Pharmacogenetics Study. Patients received GH-treatment for 12 months with finished dose-titration of GH and centralized IGF-1 measurements. GH-dose after 1 year of treatment, IGF-1 concentrations, IGF-1-standard deviation score (SDS), the IGF-1:GH ratio and anthropometric data were analyzed by genotype. Except for rs1019731, which showed a significant difference of IGF-1-SDS by genotypes (p = 0.02), all polymorphisms showed no associations with the GH-doses, IGF-1 concentrations, IGF-1-SDS and IGF-1:GH ratio after adjusting for the confounding variables gender, age and BMI. gene polymorphisms were not associated with the responsiveness to exogenous GH in GHD. Therefore, genetic variations of the gene seem not to be major influencing factors of the GH-–IGF-axis causing variable response to exogenous GH-treatment.