Association of BDNF with anorexia, bulimia and age of onset of weight loss in six European populations

Abstract

Several genes with an essential role in the regulation of eating behavior and body weight are considered candidates involved in the etiology of eating disorders (ED), but no relevant susceptibility genes with a major effect on anorexia nervosa (AN) or bulimia nervosa (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 in Spanish patients. Another single nucleotide polymorphism 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 UK) 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 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 with the pathophysiology of ED in different populations and support a role for BDNF in the susceptibility to aberrant eating behaviors.

A Large Case–Control Study of Common Functional SLC6A4 and BDNF Variants in Obsessive–Compulsive Disorder

“…Likewise, with regard to a possible SLC6A4-BDNF interaction in OCD, comorbidity in particular with major depressive disorder, might also help explain the lack of replication in our study with the previous strong finding of a protective effect of the BDNF Met66 allele in OCD by Hall et al (2003). TheV66M polymorphism has been reported in several studies as significantly associated with different depressive disorders (Angelucci et al, 2005), and well as with schizophrenia (Neves-Pereira et al, 2005), and anorexia nervosa (Ribases et al, 2004).…”

Family trios analysis of common polymorphisms in the obestatin/ghrelin, BDNF and AGRP genes in patients with Anorexia nervosa: Association with subtype, body-mass index, severity and age of onset

“…Case-control studies showed interpopulation variations ranging from no association with eating disorders in a german population (Friedel et al, 2005) and in a dutch population (de Krom et al, 2005), association with different subtypes of anorexia nervosa or bulimia nervosa in Spanish and Japanese samples (Ribases et al, 2003;Koizumi et al, 2004), to association with both eating disorders in a joint analysis of five European countries' populations (Ribases et al, 2004). This last study included a french population of 163 anorexics which showed an excess of Met66BDNF allele, especially in the ANB group, compared to a group of 510 control subjects including 56…”

“…Moreover, since ghrelin regulates AgRP orexigenic neurons and the Ala67Thr polymorphism of AgRP (Thr67AGRP) has been associated with AN (Vink et al, 2001), and also since BDNF has been involved in body weight regulation and its Val66Met polymorphism (Met66BDNF) associated with AN (Ribases et al, 2003;Ribases et al, 2004;Hashimoto et al, 2005;Ribases et al, 2005), these polymorphisms were analysed.…”

Relevance of animal models to human eating disorders and obesity

“…Specifically, the contribution of the serotoninergic system to anxious and depressive traits, which may be partially responsible for the variability in the psychopathology of BN, has been explored (Frieling et al 2006;Monteleone et al 2006a). With respect to other regulators (Ribases et al 2004), the Met66 allele of the Val66Met of the BDNF variant was found to be associated with AN and BN. To our knowledge, a model of BN based on single gene mutations or quantitative trait loci in animals has not been developed.…”