Contribution of NTRK2 to the genetic susceptibility to anorexia nervosa, harm avoidance and minimum body mass index.
Anorexia nervosa (AN) and bulimia nervosa (BN) are eating disorders (ED) with complex genetic and environmental components. Genetic studies and animal models support the participation of brain-derived neurotrophic factor (BDNF) in the vulnerability to AN and BN. We investigated the genetic contribution of the BDNF-specific receptor neurotrophic tyrosine kinase receptor type 2 (NTRK2) to the susceptibility to ED. We have screened the entire NTRK2 gene in 91 patients with ED and have identified 14 single-nucleotide polymorphisms (SNPs). A population-based association study with six SNPs from the NTRK2 locus was performed in 164 ED patients and 121 controls. Significant evidence of association for markers -69C>G and IVS13+40G>A was detected. We also observed a strong association between the C-A-insC haplotype (-69/IVS13+40/2784-2785) and binge-eating/purging AN (ANP, P=0.006; OR=2.27), and a reduced frequency of haplotype G-A-delCl in BN patients (P=0.034; OR=0.6). The analysis of ED-related phenotypes revealed a clear association between NTRK2, high scores of Harm avoidance measured by the temperament and character inventory (TCI-R; P=0.003) and minimum body mass index (minBMI; P<0.001). Our data support a contribution of NTRK2 to the genetic susceptibility of ED, mainly ANP, and ED-related phenotypic traits, such as Harm avoidance and minBMI.
Ribases
M
M
Genes and Disease Program, Center for Genomic Regulation, Barcelona, Catalonia, Spain.
Gratacos
M
M
Badia
A
A
Jimenez
L
L
Solano
R
R
Vallejo
J
J
Fernandez-Aranda
F
F
Estivill
X
X
D000328:Adult; D000856:Anorexia Nervosa / Q000235:genetics*; D001362:Avoidance Learning; D015992:Body Mass Index; D002032:Bulimia / Q000235:genetics; D002874:Chromosome Mapping; D005091:Exons; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007438:Introns; D008297:Male; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D018807:Polymorphism, Single-Stranded Conformational; D020813:Receptor, trkB / Q000235:genetics*; D012016:Reference Values; D012309:Risk-Taking
D020813:Receptor, trkB