1. ¹Genes and Disease Program, Center for Genomic Regulation, Barcelona, Catalonia, Spain
2. ²Department of Psychiatry, Hospital Princeps d'Espanya, Ciutat Sanitaria Bellvitge, L'Hospitalet de Llobregat, Barcelona, Catalonia, Spain
3. ³Pompeu Fabra University, Barcelona, Catalonia, Spain

Correspondence: X Estivill, MD, PhD, Genes and Disease Program, Center for Genomic Regulation, Passeig Maritim, 37-49, E08003 Barcelona, Catalonia, Spain. E-mail: Xavier.Estivill@crg.es

Received 17 March 2004; Revised 25 February 2005; Accepted 3 March 2005; Published online 19 April 2005.

Abstract

Anorexia nervosa (AN) and bulimia nervosa (BN) are eating disorders (ED) with complex genetic and environmental components. Genetic studies and animal models support the participation of brain-derived neurotrophic factor (BDNF) in the vulnerability to AN and BN. We investigated the genetic contribution of the BDNF-specific receptor neurotrophic tyrosine kinase receptor type 2 (NTRK2) to the susceptibility to ED. We have screened the entire NTRK2 gene in 91 patients with ED and have identified 14 single-nucleotide polymorphisms (SNPs). A population-based association study with six SNPs from the NTRK2 locus was performed in 164 ED patients and 121 controls. Significant evidence of association for markers –69C>G and IVS13+40G>A was detected. We also observed a strong association between the C-A-insC haplotype (–69/IVS13+40/2784–2785) and binge-eating/purging AN (ANP, P=0.006; OR=2.27), and a reduced frequency of haplotype G-A-delCl in BN patients (P=0.034; OR=0.6). The analysis of ED-related phenotypes revealed a clear association between NTRK2, high scores of Harm avoidance measured by the temperament and character inventory (TCI-R; P=0.003) and minimum body mass index (minBMI; P<0.001). Our data support a contribution of NTRK2 to the genetic susceptibility of ED, mainly ANP, and ED-related phenotypic traits, such as Harm avoidance and minBMI.