Article

Association of BDNF with restricting anorexia nervosa and minimum body mass index: a family-based association study of eight European populations.

Genes and Disease Program, Center for Genomic Regulation, Barcelona Biomedical Research Park, Barcelona, Spain.
European Journal of HumanGenetics (Impact Factor: 4.23). 05/2005; 13(4):428-34. DOI: 10.1038/sj.ejhg.5201351
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ABSTRACT Eating disorders (ED), such as anorexia nervosa (AN) and bulimia nervosa (BN), are complex psychiatric disorders where different genetic and environmental factors are involved. Several lines of evidence support that brain-derived neurotrophic factor (BDNF) plays an essential role in eating behaviour and that alterations on this neurotrophic system participates in the susceptibility to both AN and BN. Accordingly, intraventricular administration of BDNF in rats determines food starvation and body weight loss, while BDNF or its specific receptor NTRK2 knockout mice develop obesity and hyperphagia. Case-control studies also suggest a BDNF contribution in the aetiology of ED: we have previously reported a strong association between the Met66 variant within the BDNF gene, restricting AN (ANR) and minimum body mass index (minBMI) in a Spanish sample, and a positive association between the Val66Met and -270C/T BDNF SNPs and ED in six different European populations. To replicate these results, avoiding population stratification effects, we recruited 453 ED trios from eight European centres and performed a family-based association study. Both haplotype relative risk (HRR) and haplotype-based haplotype relative risk (HHRR) methods showed a positive association between the Met66 allele and ANR. Consistently, we also observed an effect of the Met66 variant on low minBMI and a preferential transmission of the -270C/Met66 haplotype to the affected ANR offspring. These results support the involvement of BDNF in eating behaviour and further suggest its participation in the genetic susceptibility to ED, mainly ANR and low minBMI.

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    • " have been reported to be decreased in obese compared with lean subjects ( El - Gharbawy et al . , 2006 ) and elevated in obese diabetic patients compared with controls ( Suwa et al . , 2006 ) . This neurotrophin has also been associated with eating disorders related to severe psychiatric symptoms such as in patients affected by anorexia nervosa ( Ribases et al . , 2005 ) ; its involvement in metabolic syndrome remains controversial ( Bullo , Peeraully , Trayhurn , Folch , & Salas - Salvado , 2007 ; Suwa et al . , 2006 ) . Very recent evidence show that pre - pubertal obese children tend to have decreased plasma BDNF levels than lean controls although the exact role of BDNF in the physiopathology of ob"
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    • "Here, the case–control study from Ribases et al. (2004a) has been replaced with the trio study performed on a partially overlapping sample. Ribases et al. (2004b) and Dardennes et al. (2007) are family-based, the remaining studies have a case–control design. The whiskers represent (cumulative) 95% confidence intervals. "
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