PMID- 12888803 OWN - NLM STAT- MEDLINE DCOM- 20040401 LR - 20131121 IS - 1359-4184 (Print) IS - 1359-4184 (Linking) VI - 8 IP - 8 DP - 2003 Aug TI - Met66 in the brain-derived neurotrophic factor (BDNF) precursor is associated with anorexia nervosa restrictive type. PG - 745-51 AB - 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. FAU - Ribases, M AU - Ribases M AD - Genes and Disease Program, Center for Genomic Regulation, Barcelona, Catalonia, Spain. FAU - Gratacos, M AU - Gratacos M FAU - Armengol, L AU - Armengol L FAU - de Cid, R AU - de Cid R FAU - Badia, A AU - Badia A FAU - Jimenez, L AU - Jimenez L FAU - Solano, R AU - Solano R FAU - Vallejo, J AU - Vallejo J FAU - Fernandez, F AU - Fernandez F FAU - Estivill, X AU - Estivill X LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Mol Psychiatry JT - Molecular psychiatry JID - 9607835 RN - 0 (Brain-Derived Neurotrophic Factor) RN - AE28F7PNPL (Methionine) SB - IM MH - Adult MH - Anorexia Nervosa/*genetics MH - Body Mass Index MH - Brain-Derived Neurotrophic Factor/*genetics MH - Bulimia/genetics MH - Case-Control Studies MH - Female MH - Gene Frequency MH - Genetic Predisposition to Disease MH - Genotype MH - Humans MH - Male MH - Methionine/genetics MH - Phenotype MH - Polymerase Chain Reaction MH - *Polymorphism, Single Nucleotide MH - Polymorphism, Single-Stranded Conformational EDAT- 2003/07/31 05:00 MHDA- 2004/04/02 05:00 CRDT- 2003/07/31 05:00 PHST- 2003/07/31 05:00 [pubmed] PHST- 2004/04/02 05:00 [medline] PHST- 2003/07/31 05:00 [entrez] AID - 4001281 [pii] AID - 10.1038/sj.mp.4001281 [doi] PST - ppublish SO - Mol Psychiatry. 2003 Aug;8(8):745-51. doi: 10.1038/sj.mp.4001281.