Altered brain-derived neurotrophic factor blood levels and gene variability are associated with anorexia and bulimia

Authors

  • J. M. Mercader,

    1. Genes and Disease Program, Center for Genomic Regulation, Barcelona Biomedical Research Park, Barcelona, Catalonia
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  • M. Ribasés,

    1. Genes and Disease Program, Center for Genomic Regulation, Barcelona Biomedical Research Park, Barcelona, Catalonia
    2. Department of Psychiatry, Hospital Universitari Vall d’Hebron, Universitat Autonoma de Barcelona, Catalonia
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  • M. Gratacòs,

    1. Genes and Disease Program, Center for Genomic Regulation, Barcelona Biomedical Research Park, Barcelona, Catalonia
    2. National Center of Genotyping (CEGEN), Barcelona Node, Barcelona, Catalonia
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  • J. R. González,

    1. Genes and Disease Program, Center for Genomic Regulation, Barcelona Biomedical Research Park, Barcelona, Catalonia
    2. National Center of Genotyping (CEGEN), Barcelona Node, Barcelona, Catalonia
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  • M. Bayés,

    1. Genes and Disease Program, Center for Genomic Regulation, Barcelona Biomedical Research Park, Barcelona, Catalonia
    2. National Center of Genotyping (CEGEN), Barcelona Node, Barcelona, Catalonia
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  • R. De Cid,

    1. Genes and Disease Program, Center for Genomic Regulation, Barcelona Biomedical Research Park, Barcelona, Catalonia
    2. National Center of Genotyping (CEGEN), Barcelona Node, Barcelona, Catalonia
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  • A. Badía,

    1. Department of Psychiatry, University Hospital of Bellvitge, L’Hospitalet de Llobregat, Catalonia
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  • F. Fernández-Aranda,

    1. Department of Psychiatry, University Hospital of Bellvitge, L’Hospitalet de Llobregat, Catalonia
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  • X. Estivill

    Corresponding author
    1. Genes and Disease Program, Center for Genomic Regulation, Barcelona Biomedical Research Park, Barcelona, Catalonia
    2. National Center of Genotyping (CEGEN), Barcelona Node, Barcelona, Catalonia
    3. Experimental and Health Sciences Department, Pompeu Fabra University, Barcelona, Catalonia, Spain
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*X. Estivill, Genes and Disease Program, Center for Genomic Regulation (CRG), Passeig Maritim, 37-49, 08003 Barcelona, Catalonia, Spain. E-mail: xavier.estivill@crg.es

Abstract

Murine models and association studies in eating disorder (ED) patients have shown a role for the brain-derived neurotrophic factor (BDNF) in eating behavior. Some studies have shown association of BDNF −270C/T single-nucleotide polymorphism (SNP) with bulimia nervosa (BN), while BDNF Val66Met variant has been shown to be associated with both BN and anorexia nervosa (AN). To further test the role of this neurotrophin in humans, we screened 36 SNPs in the BDNF gene and tested for their association with ED and plasma BDNF levels as a quantitative trait. We performed a family-based association study in 106 ED nuclear families and analyzed BDNF blood levels in 110 ED patients and in 50 sib pairs discordant for ED. The rs7124442T/rs11030102C/rs11030119G haplotype was found associated with high BDNF levels (mean BDNF TCG haplotype carriers = 43.6 ng/ml vs. mean others 23.0 ng/ml, P = 0.016) and BN (Z = 2.64; P recessive = 0.008), and the rs7934165A/270T haplotype was associated with AN (Z =−2.64; P additive = 0.008). The comparison of BDNF levels in 50 ED discordant sib pairs showed elevated plasma BDNF levels for the ED group (mean controls = 41.0 vs. mean ED = 52.7; P = 0.004). Our data strongly suggest that altered BDNF levels modulated by BDNF gene variability are associated with the susceptibility to ED, providing physiological evidence that BDNF plays a role in the development of AN and BN, and strongly arguing for its involvement in eating behavior and body weight regulation.

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