Growth hormone dose in growth hormone-deficient adults is not associated with IGF-1 gene polymorphisms

Abstract

Aims: Several SNPs and a microsatellite cytosine-adenine repeat promoter polymorphisms of the IGF-1 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-defecient patients. The aim of this study was to test if the IGF-1 gene polymorphisms are associated with the GH-dose of GH-defecient adults. Materials & methods: A total of nine SNPs, five addtionally 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 stamdard 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 genotyped. Results: 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 ration after adjusting for the confounding variabl