Sequencing analysis of the ghrelin receptor (growth hormone secretagogue receptor type 1a) gene

Department of Internal Medicine and Biocenter Oulu, University of Oulu, PO Box 5000, 90014 Oulu, Finland.

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.

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