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Met66 in the brain-derived neurotrophic factor (BDNF) precursor is associated with anorexia nervosa restrictive type

Molecular Psychiatry volume 8, pages 745–751 (2003)Cite this article

Abstract

Several lines of evidence support a role for brain-derived neurotrophic factor (BDNF) alterations in the etiology of eating disorders (EDs). BDNF heterozygous knockout mice show alterations in eating behavior, increased body weight and adipocyte hypertrophy. BDNF also regulates the synaptic efficiency through the modulation of key neurotransmitter systems previously known to be involved in ED. These findings, together with the fact that this neurotrophin is expressed in the hypothalamus nuclei associated with weight regulation and feeding control, led us to propose BDNF as a candidate gene for ED. To investigate the possible involvement of this neurotrophin in eating behavior, we screened the BDNF gene in 95 ED patients and identified four sequence variants. Two of them, −374A/T and −256G/A, were found in two patients with anorexia nervosa (AN) and consisted of single-nucleotide mutations within the 5′ untranslated region (5′UTR). The other two polymorphisms resulted in a C to T transition located at the 5′UTR of the BDNF gene and an amino-acid substitution within the BDNF precursor protein (Val66Met). We performed a case–control study for these two Single-nucleotide polymorphisms in a sample of 143 ED patients and 112 unrelated controls and found a strong association of restricting AN (ANR) with the Met allele of the Val66Met BDNF polymorphism (2p=0.002). There was also evidence for a significant effect of this sequence variant on the minimum body mass index (MBMI) (2p=0.006). These results suggest that the BDNF Met66 variant may be a susceptibility factor to ED, mainly to ANR and low MBMI.

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Acknowledgements

We thank the patients for their participation in the study, and M Dierssen and H Kruyer for their helpful comments on the manuscript. MR is supported by the Fondo de Investigaciones Sanitarias de la Seguridad Social (FISS), Instituto de Salud Carlos III. MG is supported by the EU (ECF5000916). XE is a Senior Scientist of the Centre de Regulació Genòmica (CRG). Financial support was received from the European Union (Framework-V Multicentre Research Grant, QLK1-1999-916) for FF and XE, from the Red FIS G03/184 and from the Departament d'Universitats Recerca i Societat de la Informació (DURSI) and the Departament de Sanitat for XE.

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Authors and Affiliations

  1. Genes ad Disease Program, Center for Genomic Regulation, Barcelona, Spain

    M Ribasés, M Gratacòs, L Armengol, R de Cid & X Estivill

  2. Medical and Molecular Genetics Center—IRO, Barcelona, Spain

    M Ribasés, L Armengol, R de Cid & X Estivill

  3. Fundació August Pi i Sunyer, Ciutat Sanitària Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain

    M Gratacòs

  4. Servei de Psiquiatria, Hospital de Bellvitge, Ciutat Sanitària Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain

    A Badía, L Jiménez, R Solano, J Vallejo & F Fernández

  5. Departament de Ciències de la Salut i de la Vida, Universitat Pompeu Fabra, Barcelona, Spain

    X Estivill

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  1. M Ribasés
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Correspondence to X Estivill.

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Ribasés, M., Gratacòs, M., Armengol, L. et al. Met66 in the brain-derived neurotrophic factor (BDNF) precursor is associated with anorexia nervosa restrictive type. Mol Psychiatry 8, 745–751 (2003). https://doi.org/10.1038/sj.mp.4001281

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