Altered brain-derived neurotrophic factor blood levels and gene variability are associated with anorexia and bulimia.
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.
Mercader
J M
JM
Genes and Disease Program, Center for Genomic Regulation, Barcelona Biomedical Research Park, Barcelona, Catalonia, Spain.
Ribasés
M
M
Gratacòs
M
M
González
J R
JR
Bayés
M
M
de Cid
R
R
Badía
A
A
Fernández-Aranda
F
F
Estivill
X
X
D000293:Adolescent; D000328:Adult; D000856:Anorexia Nervosa / Q000097:blood / Q000235:genetics*; D001835:Body Weight / Q000235:genetics*; D019208:Brain-Derived Neurotrophic Factor / Q000097:blood / Q000235:genetics*; D052018:Bulimia Nervosa / Q000097:blood / Q000235:genetics*; D016022:Case-Control Studies; D005247:Feeding Behavior / Q000502:physiology*; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D012016:Reference Values; D016037:Single-Blind Method; D018709:Statistics, Nonparametric
D019208:Brain-Derived Neurotrophic Factor