OBJECTIVES AND DESIGN: Ghrelin is a novel 28 amino acid peptide which is reported to have several endocrine and non-endocrine actions. It possesses strong growth hormone (GH)-releasing activity, which is mediated via the GH secretagogue receptor type 1a (GHS-R1a). We hypothesised that there might be functional sequential variations in the GHS-R1a gene affecting phenotypes linked to the GH/insulin-like growth factor-I (IGF-I)-axis. METHODS: To test our hypothesis we chose patients from our OPERA (Oulu Project Elucidating Risk of Atherosclerosis) study with low (n=96) and high (n=96) IGF-I levels, sequenced their GHS-R1a gene exons and performed association studies. RESULTS: We found five single-nucleotide polymorphisms (SNPs) which did not change the amino acid sequence. We were unable to detect associations between the SNPs and the IGF-I plasma concentrations, but instead we showed that SNP 171C>T was associated with the values of the area under the insulin curve (AUCIN) in an oral glucose tolerance test and with IGF-binding protein-1 (IGFBP-1) concentrations (P<0.05). SNP 477G>A was associated with the low density lipoprotein and very low density lipoprotein cholesterol plasma levels and AUCIN values (P<0.05). CONCLUSIONS: This study was the first genomic screening of the GHS-R1a gene in a population. It suggests that genetic variations in the GHS-R1a gene are not the main regulators of IGF-I levels. However, the variants may be associated with IGFBP-1 concentrations and insulin metabolism.