Molecular studies on preproghrelin gene: Signal peptide, ghrelin coding region and variants – A brief report focusing on rs34911341 polymorphism

Abstract

Background: Ghrelin is a hormone that exhibits effects in a lot of biologic processes, such as food intake regulation, gastrointestinal motility and carbohydrate metabolism. Ghrelin is encoded by human preproghrelin gene (GHRL), reported with four exons. However, experiments suggested a new molecular structure for this gene. Objective: This study aims to clarify by a simple representation GHRL and its products, showing the variants described for this gene up to this moment. Methods: The GHRL sequence for molecular comparisons was obtained from GeneBank. The dbSNP was used to search variants and the PubMed, Scielo and Science Direct databases to investigate related studies. Results: The new molecular structure of GHRL includes a new exon 0 and an extended exon 1, located in the originally identified region of intron 1. Examples of GHRL products are signal, ghrelin and obestatin peptides and these molecules exhibit different effects on the organism. Thus, polymorphisms in these gene regions have been associated with a vast number of clinical effects, including metabolic disorders. We identified 11 genetic variations in the region of the GHRL which encodes for the signal peptide and 23 polymorphisms in the ghrelin coding region. One of them, rs34911341, has been associated with some disorders such as diabetes, hypertension and obesity. Conclusion: In this scientific article we turned GHRL a little bit more informative for readers. Furthermore we highlighted the current reported GHRL genetic variations associated to signal and ghrelin peptides, but only the variant rs34911341 has been associated with metabolic disorders.

Computational Investigation of the Impact of the Ghrelin Hormone Gene Variation (R51q) on the Hormone-receptor Binding Pattern

“…In conclusion, the ghrelin gene variation R51Q was previously investigated clinically, and it was found to be associated with metabolic syndrome, 13,30 hypertension, 31 obesity, 32 and gastric cancer. 33 In the current study, it was revealed that this mutation did not result in observable conformational changes in the C-terminal of the ghrelin model hormone, but it did affect the final stability of the complex by generating new molecular interactions between the ligand and receptor models followed by decreased its total energy.…”

“…The arginine residue at position 28 of the mature ghrelin hormone was thought to be essential for endoprotease identification and action. 13 Endoprotease catalyzes the proteolytic cleavage during the production of ghrelin. 14,15 Yet, it is unclear if this genetic variation alters ghrelin's physiologic characteristics or action.Ghrelin and ghrelin receptor agonists can effectively treat anorexia and cachexia in cancer 16,17 and chronic kidney disease patients.…”