Human Molecular Genetics Advance Access published online on April 28, 2004
Human Molecular Genetics, doi:10.1093/hmg/ddh137
© 2004 by Oxford University Press
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1 Genes and Disease Program, Center for Genomic Regulation, Barcelona Biomedical Research Park, Barcelona, Spain
* To whom correspondence should be addressed. E-mail: xavier.estivill{at}crg.es.
Several genes with an essential role in the regulation of eating behavior and body weight are considered candidates to participate in eating disorders (ED), but no relevant susceptibility genes with a major effect on anorexia (AN) or bulimia (BN) have been identified. Brain-derived neurotrophic factor (BDNF) has been implicated in the regulation of food intake and body weight in rodents. We previously reported a strong association of the Met66 allele of the Val66Met BDNF variant with restricting AN (ANR) and low minimum body mass index (minBMI) in Spanish patients. Another single nucleotide polymorphism (SNP) located in the promoter region of the BDNF gene (-270C/T) showed lack of association with any ED phenotype. In order to replicate these findings in a larger sample, we performed a case-control study in 1142 Caucasian patients with ED consecutively recruited in six different centers from five European countries (France, Germany, Italy, Spain and United Kingdom) participating in the "Factors in Healthy Eating" project. We have found that the Met66 variant is strongly associated to all ED subtypes (AN, ANR, binge-eating/purging AN (ANP) and BN), and that the -270C BDNF variant has an effect on BN and late age at onset of weight loss. These are the first two variants associated to the pathophysiology of ED in different populations and support a role of BDNF in the susceptibility to aberrant eating behaviors.
Article
Association of BDNF with Anorexia, Bulimia and age of onset of weight loss in six European populations
2 Department of Psychiatry, Hospital Principes d'España, L'Hospitalet de Llobregat, Barcelona, Spain
3 Department of Neuropsychiatric Sciences (DSNP), Fondazione Centro S. Raffaele del Monte Tabor, Milan, Italy
4 INSERM U 288, Neuropsychopharmacologie, CHU Pitié-Salpêtrière, Paris, France
5 University Psychiatric Hospital Ljubljana, Slovenia
6 University of Florence, Department of Neurology and Psychiatric Sciences, Viale Morgagni 85, 50134 Florence, Italy
7 CMME. Centre Hospitalier Sainte-Anne, 100 rue de la Santé, Paris, France
8 Medical Centre for Molecular Biology (MCMB), Faculty of Medicine, University of Ljubljana, Slovenia
9 Hôpital Louis Mourier (AP-HP), Service de Psychiatrie, 178 rue des Renouillers, Colombes, France
10 Clinical Research Group, Department of Child and Adolescent Psychiatry, Philipps University Marburg, Germany
11 Eating Disorders Unit and SGDP Research Centre, Institute of Psychiatry, De Crespigny Park, Denmark Hill, London SE5 8AF, UK
12 University Clinic of Neuropsychiatry of Childhood and Adolescence, Waehringer Guertel 18-20 A-1090, Vienna, Austria
13 CNRS UMR 7593-Paris VII, Personnalité et Conduites Adaptatives, CHU Pitié-Salpêtrière, Paris, France
14 Genes and Disease Program, Center for Genomic Regulation (CRG), Barcelona Biomedical Research Park, Passeig Maritim, 37-49, 08003 Barcelona, Catalonia, Spain; Experimental and Helth Sciences Department, Pompeu Fabra University, Barcelona Biomedical Research Park, Barcelona, Spain
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