articleBDNF Val 66 Met polymorphism , energy intake and BMI : a follow-up study in schoolchildren at risk of eating disorders

Background: Eating disorders (ED) have a multifactorial aetiology in which genetics play an important role. Several studies have found an association between the Val66Met (G196A) polymorphism of the Brain-Derived Neurotrophic Factor (BDNF) and Eating disorders. The aim of this study was to determine the association of the Val66Met (G196A) polymorphism of the BDNF gene and its effect on eating disorders (ED), energy intake and BMI in schoolchildren. Methods: Two-year cohort study (preadolescence to adolescence). From an initial sample of 1336 Caucasian children (mean age = 11.37 years), a group at risk of ED (n = 141) and a control group (n = 117) were selected using the Children's Eating Attitudes Test. Two years later, they were re-classified into an at-risk group (n = 41) and a control group (n = 159) using the Eating Attitudes Test. The diagnosis of the individuals at risk of ED was confirmed by means of the Diagnostic Interview for Children and Adolescents. BMI, energy intake and the Val66Met (G196A) polymorphism of the BDNF gene were analysed in the at-risk and control groups. Results: The frequency of genotypes of the Val66Met (G196A) polymorphism of the BDNF gene is 28.6% (95% CI: 22.434.9) in the heterozygous form (Val/Met) and 5% (95% CI: 2.4-9) in the homozygous form (Met/Met). We detected no association between Val66Met genotypes and the severity of ED. Over time, the carriers of the Met66 allele with a persistent risk of ED significantly restricted energy intake (507 Kcal/day; p = 0.033). Conclusion: We have not found an association between Val66Met (G196A) polymorphism of the BDNF and ED in schoolchildren from general population. The relationship found between this polymorphism and energy intake restriction in adolescents with a persistent risk of ED should be replicated in a larger sample. Background Eating disorders (ED) have a multifactorial aetiology and negatively affect both the psychosocial and developmental levels. A high proportion of adolescents--between 20% and 25%--have inappropriate attitudes towards weight control [1-3]. The continuity hypothesis of ED supported by Vanderheyden and Boland [4] suggests that risky attitudes could be responsible for ED [5,6] and may be related to the same biological and personality characteristics that are present in full-blown syndromes. Many studies have investigated the role of genetics in ED. Brain-derived neurotrophic factor (BDNF) is a protein belonging to the neurotrophin family that is involved in the proliferation, differentiation and survival of neurons in the nervous system [7]. In the past few years, it has generated considerable interest because of its distribution in the key brain regions that are involved in behaviour, energy homeostasis and weight control. Furthermore, BDNF provides trophic support to noradrenergic, dopaminergic and serotonergic neurons, among others [8], whose neurotransmitters are altered in many mental illnesses. Some researchers have hypothesised that neurotrophins are involved in mental illnesses because of an alteration in synaptic plasticity [9,10], in which BDNF plays a fundamental role. This synaptic alteration could be due to the Val66Met (G196A) polymorphism of the BDNF gene (MIM 113505), which alters * Correspondence: josefa.canals@urv.cat 2 CRAMC, Departament de Psicologia. Universitat Rovira i Virgili, Spain Full list of author information is available at the end of the article © 2010 Arija et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Arija et al. BMC Public Health 2010, 10:363 http://www.biomedcentral. com/1471-2458/10/363 Page 2 of 11 how the secretion of mature BDNF is regulated [11,12]. This polymorphism (Single Nucleotide Polymorphism database (dbSNP) rs6265) is located on chromosome 11p13-11p14 [13], which encodes the peptide precursor (proBDNF) of BDNF. Restricting anorexia nervosa (AN) and minimum body mass index (BMI) has been associated with the aforementioned Val66Met (G196A) polymorphism of the BDNF gene, and it has been suggested that the A allele (Met) may affect susceptibility to ED [14,15]. In a broad population from six samples in five European countries, consisting mainly of women aged 20-30, the association of the polymorphism was extended to all kinds of ED, including restricting AN (ANR), binge-eating AN (ANB) and bulimia nervosa (BN) [14]. In Japan, Koizumi et al [16] observed significant differences between the genotypes of the Val66Met (G196A) polymorphism in female patients with ED (EDNOS, AN and BN) and those of control participants. When observed separately, however, significant differences were found only in the distribution of genotypes in ANR and purging BN. A significant association was also found between a higher score on the Bulimic Investigatory Test, Edinburgh (BITE) and the AA genotype (Met/Met) in patients with BN and binge ED [17]. A recent meta-analysis study [18] suggested that Caucasian individuals aged 20-26 with Val/Met genotypes have a 36% higher risk of developing ED than those with the Val/Val genotype. However, some studies have found there to be no association in patients with ED [17,19,20]. BDNF is also known to play a key role in eating behaviour and weight regulation [21]. Both BDNF and its receptor NTRK2 are found in hypothalamic areas that are critical to feeding and energy regulation [22]. Studies carried out on animals suggest that hyperphagia affects not only the relationship between the level of BDNF and BMI [23], but also the regulation of food intake by acting as an anorexigenic factor [24,25]. Attempts have been made to establish an association between polymorphism and BMI in the general adult population of both sexes, but the results are contradictory. Compared with the Val/Met and Val/Val genotypes, the association between the Met/Met genotype and low BMI is much greater [26]. Nevertheless, contrary to the results of a recent study [27], we observed that patients with BN carrying the Met66 allele of the BDNF gene and the 7R allele of the dopamine-4 receptor gene (DRD4) have a higher BMI. Mutations in the gene that encodes the BDNF or its receptor (TrKB) may explain certain kinds of obesity or forms of ED in humans [25]. In light of the lack of research on the frequency of BDNF gene alteration in the adolescent population, the contradictory results reported to date with regard to the association between BDNF gene alteration and ED, and the main consequences of this type of alteration on energy intake and BMI, we decided to undertake a longitudinal study to clarify these aspects. The objectives of our study were: a) to determine the relation between the frequency of the Val66Met (G196A) polymorphism of the BDNF gene and the severity of risk of ED, b) to establish the association between genetic alteration and risk of ED, and c) to study the effects of this genetic alteration on BMI and energy intake according to the evolution of the risk of ED.