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

Abstract

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 ¼ 96) and high (n ¼ 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.

Association Studies on Ghrelin and Ghrelin Receptor Gene Polymorphisms With Obesity

“…Genetic linkage and association between single‐nucleotide polymorphisms (SNPs) and haplotypes within the GHSR gene region (locus 3q26.2) with obesity have been reported by Baessler et al (15). Genetic studies for the reported individual SNPs in ghrelin and GHSR genes failed, however, to show consistent results with obesity or insulin resistance (22,23,24,25,58,65,66,67).…”

Molecular Characterization of the Ghrelin and Ghrelin Receptor Genes and Effects on Fat Deposition in Chicken and Duck

“…In humans, a total of 11 SNPs were found in 1657 bp of GHRL gene with an SNP density of 1 SNP/151 bp [13]. The reported density for the human GHSR gene (5 SNP of 1101 bp) was 220 bp per SNP [37]. Based on the dbSNP data (http://www.ncbi.nlm.nih.gov), a total of 8 and 32 SNPs were reported in 2922 and 6494 bp of the mouse GHRL and GHSR genes, with estimated densities of 365 and 203 bp per SNP, respectively.…”

Variations in the Ghrelin Receptor Gene Associate with Obesity and Glucose Metabolism in Individuals with Impaired Glucose Tolerance

“…Vartiainen et al [16] showed that subjects with rs495225-CC genotype had highest area under the insulin curve values and IGFBP-1 concentrations. In the present study, in the DPS population rs6772767, rs490683 and rs509035 were associated with several measures of glucose metabolism over four consecutive measurements.…”

“…Baessler et al have described a “susceptible” and “non-susceptible” haplotype for obesity of five GHSR single nucleotide polymorphisms (SNPs) [15]. Vartiainen et al [16] showed an association between insulin values and a GHSR variant. A recent study reports a weak association between one GHSR variant and BMI [17].…”