Background/Aims: Expression of the human growth hormone (GH) gene (GH1) is regulated by a locus control region (LCR) and the highly polymorphic GH1 promoter. We analyzed GH1 LCR/promoter single nucleotide polymorphisms (SNPs) in patients with isolated growth hormone deficiency (IGHD) in relation to clinical data. Methods: We directly sequenced the GH1 LCR/promoter of 62 Dutch IGHD patients without mutations or deletions in GH1 or GHRHR and of 72 controls with normal height. We related GH1 LCR/promoter SNPs to height, serum insulin-like growth factor 1 (IGF-I) levels and response to GH treatment. Results: In IGHD patients, promoter SNPs 6, 8 and 9 were associated with height and IGF-1 levels. In controls, SNPs 6 and 11 were associated with height. Homozygosity for the minor allele of SNP 9, associated with lower IGF-I levels in patients, was significantly more frequent among patients than among controls. Genotypes based on SNPs 6, 8, 9 and 11 explained 10.8% of IGF-I SDS variation in IGHD patients and 15.9% of height SDS variation in controls. Conclusion:GH1 Promoter SNPs 6, 8 and 9 were associated with height and IGF-1 levels among patients, and SNPs 6 and 11 with height in controls. Copyright

Growth hormone, Insulin-like growth factor 1, Locus control region, Promoter, Single nucleotide polymorphism,
Hormone Research in Paediatrics
Erasmus MC: University Medical Center Rotterdam

de Graaff, L.C.G, Argente, J, van Meurs, J.B.J, Uitterlinden, A.G, & Hokken-Koelega, A.C.S. (2010). Genetic polymorphisms in the locus control region and promoter of GH1 are related to serum IGF-I levels and height in patients with isolated growth hormone deficiency and healthy controls. Hormone Research in Paediatrics, 73(1), 25–34. doi:10.1159/000271913