Genetic variation of the ghrelin activator gene ghrelin O-acyltransferase (GOAT) is associated with anorexia nervosa.

Abstract

The gastrointestinal peptide hormone ghrelin promotes food intake and increases body weight and adiposity through activation of the growth hormone secretagogue receptor (GHSR1a). To promote its biological action ghrelin is acylated at its serine 3 residue by the recently discovered ghrelin O-acyltransferase (GOAT, a.k.a. membrane-bound O-acyltransferase 4, MBOAT4). Plasma levels of total and acyl-ghrelin are negatively correlated with body-mass-index (BMI); as lower the BMI as higher plasma levels of total and acylated ghrelin and vice versa. Accordingly, plasma levels of total and acyl-ghrelin are elevated in patients with anorexia nervosa (AN) and decline upon weight regain. The importance of the endogenous Goat/ghrelin system in the neuroendocrine adaptation to fasting was recently highlighted by the observation that acyl-ghrelin mediated elevation of growth hormone (GH) release prevents starvation induced hypoglycemia in Goat(-/-) mice. The aim of this study was to test if genetic variation of GOAT is implicated in the etiology of AN. We therefore assessed association of 6 tagging single nucleotide polymorphisms (tagSNPs), which were predicted to cover 96% the common genetic variability of GOAT plus 50 kb of the 5' and 3' flanking region, in 543 German patients with AN and 612 German normal and underweight healthy controls. Based on a recessive mode of inheritance we observed some evidence for association of the G/G genotype at SNP rs10096097 with AN (nominal two-sided p = 0.031). Based on our results we conclude that genetic variation in GOAT might be implicated in the etiology of AN.

• Authors: Timo D Müller, Matthias H Tschöp, Ivonne Jarick, Stefan Ehrlich, Susann Scherag, Beate Herpertz-Dahlmann, Stefan Zipfel, Wolfgang Herzog, Martina de Zwaan, Roland Burghardt, Christian Fleischhaker, Karin Klampfl, Christoph Wewetzer, Stephan Herpertz, Almut Zeeck, Sefik Tagay, Markus Burgmer, Paul T Pfluger, André Scherag, Johannes Hebebrand, Anke Hinney
• Journal: Journal of psychiatric research (J Psychiatr Res) Vol. 45 Issue 5 Pg. 706-11 (May 2011) ISSN: 1879-1379 [Electronic] England
• PMID: 21035823 (Publication Type: Journal Article)
• Copyright: Copyright © 2010 Elsevier Ltd. All rights reserved.

Chemical References

• Acyltransferases
• MBOAT4 protein, human

Topics

• Acyltransferases (genetics)
• Anorexia Nervosa (genetics)
• Body Mass Index
• Female
• Gene Frequency
• Genetic Predisposition to Disease
• Genome-Wide Association Study
• Genotype
• Humans
• Male
• Odds Ratio
• Polymorphism, Single Nucleotide (genetics)