Association of BDNF with anorexia, bulimia and age of onset of weight loss in six European populations

被引:171
作者
Ribasés, M
Gratacòs, M
Fernández-Aranda, F
Bellodi, L
Boni, C
Anderluh, M
Cavallini, MC
Cellini, E
Di Bella, D
Erzegovesi, S
Foulon, C
Gabrovsek, M
Gorwood, P
Hebebrand, J
Hinney, A
Holliday, J
Hu, X
Karwautz, A
Kipman, A
Komel, R
Nacmias, B
Remschmidt, H
Ricca, V
Sorbi, S
Wagner, G
Treasure, J
Collier, DA
Estivill, X
机构
[1] Ctr Genom Regulat, Genes & Dis Program, Barcelona 08003, Spain
[2] Hosp LLobregat, Hosp Principes Espana, Dept Psychiat, Barcelona, Spain
[3] Fdn Ctr S Raffaele Monte Tabor, Dept Neuropsychiat Sci, Milan, Italy
[4] CHU Pitie Salpetriere, INSERM, U 288, Paris, France
[5] Univ Ljubljana, Hosp Psychiat, Ljubljana, Slovenia
[6] Univ Florence, Dept Neurol & Psychiat Sci, I-50134 Florence, Italy
[7] Ctr Hosp St Anne, CMME, Paris, France
[8] Univ Ljubljana, Fac Med, Med Ctr Mol Biol, Ljubljana 61000, Slovenia
[9] Hop Louis Mourier, Psychiat Serv, Colombes, France
[10] Univ Marburg, Dept Child & Adolescent Psychiat, Clin Res Grp, D-35032 Marburg, Germany
[11] Inst Psychiat, Eating Disorders Unit, London SE5 8AF, England
[12] Inst Psychiat, SGDP Res Ctr, London SE5 8AF, England
[13] Univ Vienna, Clin Neuropsychiat Childhood & Adolescence, A-1090 Vienna, Austria
[14] CHU Pitie Salpetriere, CNRS UMR 7593 Paris 7, Paris, France
[15] Pompeu Fabra Univ, Expt & Hlth Sci Dept, Barcelona, Spain
关键词
D O I
10.1093/hmg/ddh137
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Several genes with an essential role in the regulation of eating behavior and body weight are considered candidates involved in the etiology of eating disorders (ED), but no relevant susceptibility genes with a major effect on anorexia nervosa (AN) or bulimia nervosa (BN) have been identified. Brain-derived neurotrophic factor (BDNF) has been implicated in the regulation of food intake and body weight in rodents. We previously reported a strong association of the Met66 allele of the Val66Met BDNF variant with restricting AN (ANR) and low minimum body mass index in Spanish patients. Another single nucleotide polymorphism located in the promoter region of the BDNF gene (-270C>T) showed lack of association with any ED phenotype. In order to replicate these findings in a larger sample, we performed a case-control study in 1142 Caucasian patients with ED consecutively recruited in six different centers from five European countries (France, Germany, Italy, Spain and UK) participating in the 'Factors in Healthy Eating' project. We have found that the Met66 variant is strongly associated to all ED subtypes (AN, ANR, binge-eating/purging AN and BN), and that the -270C BDNF variant has an effect on BN and late age at onset of weight loss. These are the first two variants associated with the pathophysiology of ED in different populations and support a role for BDNF in the susceptibility to aberrant eating behaviors.
引用
收藏
页码:1205 / 1212
页数:8
相关论文
共 35 条
[11]   Alterations in serotonin activity and psychiatric symptoms after recovery from bulimia nervosa [J].
Kaye, WH ;
Greeno, CG ;
Moss, H ;
Fernstrom, J ;
Fernstrom, M ;
Lilenfeld, LR ;
Weltzin, TE ;
Mann, JJ .
ARCHIVES OF GENERAL PSYCHIATRY, 1998, 55 (10) :927-935
[12]   BDNF regulates eating behavior and locomotor activity in mice [J].
Kernie, SG ;
Liebl, DJ ;
Parada, LF .
EMBO JOURNAL, 2000, 19 (06) :1290-1300
[13]   Dietary restriction increases the number of newly generated neural cells, and induces BDNF expression, in the dentate gyrus of rats [J].
Lee, J ;
Duan, WZ ;
Long, JM ;
Ingram, DK ;
Mattson, MP .
JOURNAL OF MOLECULAR NEUROSCIENCE, 2000, 15 (02) :99-108
[14]   NEUROTROPHIC FACTORS AND SYNAPTIC PLASTICITY [J].
LO, DC .
NEURON, 1995, 15 (05) :979-981
[15]   Brain-derived neurotrophic factor-deficient mice develop aggressiveness and hyperphagia in conjunction with brain serotonergic abnormalities [J].
Lyons, WE ;
Mamounas, LA ;
Ricaurte, GA ;
Coppola, V ;
Reid, SW ;
Bora, SH ;
Wihler, C ;
Koliatsos, VE ;
Tessarollo, L .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (26) :15239-15244
[16]   Biosynthesis and post-translational processing of the precursor to brain-derived neurotrophic factor [J].
Mowla, SJ ;
Farhadi, HF ;
Pareek, S ;
Atwal, JK ;
Morris, SJ ;
Seidah, NG ;
Murphy, RA .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (16) :12660-12666
[17]   Decreased levels of serum brain-derived neurotrophic factor in female patients with eating disorders [J].
Nakazato, M ;
Hashimoto, K ;
Shimizu, E ;
Kumakiri, C ;
Koizumi, H ;
Okamura, N ;
Mitsumori, M ;
Komatsu, N ;
Iyo, M .
BIOLOGICAL PSYCHIATRY, 2003, 54 (04) :485-490
[18]  
Neeper SA, 1996, BRAIN RES, V726, P49, DOI 10.1016/0006-8993(96)00273-9
[19]  
NEEPER SA, 1995, NATURE, V373, P109, DOI 10.1038/373109a0
[20]   The brain-derived neurotrophic factor gene confers susceptibility to bipolar disorder: Evidence from a family-based association study [J].
Neves-Pereira, M ;
Mundo, E ;
Muglia, P ;
King, N ;
Macciardi, F ;
Kennedy, JL .
AMERICAN JOURNAL OF HUMAN GENETICS, 2002, 71 (03) :651-655