Common insulin-like growth factor 1 (IGF-1) gene polymorphisms are not associated with the growth hormone (GH)-dose in adults with GH-deficiency

Objective: Several single nucleotide polymorphisms (SNPs) of the insulin-like growth factor 1 (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 be responsible for different response to growth hormone (GH) treatment. Aim of this study was to test if common IGF-1 gene polymorphisms are associated with the individually required GH-dose in adults with GH-deficiency (GHD). Patients and Methods: Nine tagging and five additionally selected SNPs were determined in 133 German adult patients (66 men, 67 women; mean age 45,4 years±13,1 SD; majority Caucasian) with GHD of different origin, derived from the prospective KIMS Pharmacogenetics Study. Patients received GH-treatment for at least 12 months with finished dose-titration of GH and centralized IGF-1 measurements. GH-dose after one year of treatment, IGF-1 concentrations, IGF-1-SDS and anthropometric data were analyzed by genotype. Results: Concerning etiology, gender, age and anthropometric data, study subjects showed no significant differences by genotype. The 14 SNPs revealed likewise no significant associations with the GH-dose, IGF-1 serum concentrations, IGF-1-SDS and the IGF-1/GH ratio. Conclusion: Common IGF-1 gene polymorphisms were not associated with the responsiveness to exogenous GH in GH-deficient adults. Therefore, genetic variations of the IGF-1 gene seem not to be major influencing factors of the GH-IGF-axis causing variable response to exogenous GH-treatment.