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Genetic and epigenetic variations in BDNF gene involved in Anorexia Nervosa

Published online by Cambridge University Press:  01 September 2022

N. Ramoz ,
G. Maussion ,
J. Clarke  and
P. Gorwood
N. Ramoz*
Affiliation:
University of Paris, Ipnp, Inserm U1266, Paris, France
G. Maussion
Affiliation:
University of Paris, Ipnp, Inserm U1266, Paris, France McGill University, The Neuro’s Early Drug Discovery Unit (eddu), Montreal, Canada
J. Clarke
Affiliation:
University of Paris, Ipnp, Inserm U1266, Paris, France GHU Psychiatry & Neurosciences Paris, Clinique Des Maladies Mentales Et De L’encéphale (cmme), Centre Hospitalier Sainte-anne, Paris, France
P. Gorwood
Affiliation:
University of Paris, Ipnp, Inserm U1266, Paris, France GHU Psychiatry & Neurosciences Paris, Clinique Des Maladies Mentales Et De L’encéphale (cmme), Centre Hospitalier Sainte-anne, Paris, France
*
*Corresponding author.

Abstract

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Introduction

Anorexia nervosa (AN) is a chronic psychiatric disorder resulting from abnormal eating habits with a high prevalence (0.5%). AN involves genetic and epigenetic factors supporting that AN is a metabo-psychiatric disorder. One candidate gene for AN, validated by meta-analyzes, is BDNF which encodes the brain-derived neurotrophic factor. BDNF negatively modulates the central control of food intake and its injection in rodents induces weight loss and anorexia. In humans, we observed an association of its functional variant Val66Met/rs6265 and electrodermal response to images of thinness suggesting an association between rs6265 and a reward effect of weight loss in AN.

Objectives

This work study the impact of the functional polymorphism at risk rs6265, epigenetic variations in DNA methylation of BDNF gene and consequences on the concentrations of BDNF in AN patients.

Methods

DNA was isolated from 24 AN patients and 48 controls. DNA methylation was measured for sites spanning the BDNF gene using Infinium HumanMethylation450 BeadChip technology. The genotyping of rs6265 was performed by Taqman-SNP assay. The BDNF was dosaged by ELISA from plasmas.

Results

We observe that several sites are significantly hypermethylated in AN patients compared to controls. AN patients show significantly higher BDNF levels than controls. Finally, this BDNF concentration is significantly higher in AN carrying the risk Met66 allele.

Conclusions

This work demonstrates the effects of genetic and epigenetic variations of BDNF, which could constitute relevant diagnostic biomarkers of AN, and their likely consequences in the pathophysiology of AN. This work was supported by the Nestlé Foundation.

Disclosure

No significant relationships.

Keywords

DNA methylationNeuropsychiatrybiomarkerDosage
Type
Abstract
Information
European Psychiatry , Volume 65 , Special Issue S1: Abstracts of the 30th European Congress of Psychiatry , June 2022 , pp. S677 - S678
Creative Commons
Creative Common License - CCCreative Common License - BY
This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited.
Copyright
© The Author(s), 2022. Published by Cambridge University Press on behalf of the European Psychiatric Association
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