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

Identifieur interne : 001D36 ( Main/Exploration ); précédent : 001D35; suivant : 001D37

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

Auteurs : Johanna Vartiainen [Finlande] ; Seppo M. Pöykkö [Finlande] ; Tuija R Is Nen [Finlande] ; Y. Antero Kes Niemi [Finlande] ; Olavi Ukkola [Finlande]

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RBID : Pascal:04-0282832

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English descriptors

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 la (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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Le document en format XML

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<div type="abstract" xml:lang="en">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 la (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.</div>
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