Met66 in the brain-derived neurotrophic factor (BDNF) precursor is associated with anorexia nervosa restrictive type

Mol Psychiatry. 2003 Aug;8(8):745-51. doi: 10.1038/


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anorexia Nervosa / genetics*
  • Body Mass Index
  • Brain-Derived Neurotrophic Factor / genetics*
  • Bulimia / genetics
  • Case-Control Studies
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Male
  • Methionine / genetics
  • Phenotype
  • Polymerase Chain Reaction
  • Polymorphism, Single Nucleotide*
  • Polymorphism, Single-Stranded Conformational


  • Brain-Derived Neurotrophic Factor
  • Methionine