Background
Family, twin and molecular studies provide increasing evidence for the importance
of genetic factors in obsessive-compulsive disorder (OCD). Recent work suggests that
brain-derived neurotrophic factor (BDNF) may be involved in OCD pathophysiology. We
used a linkage disequilibrium (LD)-mapping approach to investigate the role that BDNF
and its specific receptor neurotrophic tyrosine kinase receptor type 2 (NTRK2) may
play in increasing susceptibility to OCD.
Methods
Eight tag single nucleotide polymorphisms (tagSNPs) covering the BDNF gene region
and 46 tagSNPs in the NTRK2 region were genotyped in 215 OCD patients and 342 control
subjects. Single nucleotide polymorphism association and haplotype analysis were performed.
The possible relationship between genetic factors and clinical characteristics including
age of OCD onset, tic disorders, clinical dimensions, and family history of OCD were
investigated.
Results
Haplotype analysis revealed a significant association between OCD and a five-marker
protective haplotype located toward the 5’ of the BDNF gene (odds ratio [OR] = .80;
95% confidence interval [CI] = .69–.92; permutation p value = .006) containing the functional valine (Val)66-to-methionine (Met) variant.
A significant association between a NTRK2 intronic SNP (rs2378672) and OCD was identified
(p < .0001) in female patients under an additive model. A protective haplotype located
in intron 19 of NTRK2 was also associated with OCD (OR = .76; 95% CI = .66–.87; permutation
p value = .001).
Conclusions
These findings support a role for the BDNF/NTRK2 signaling pathway in genetic susceptibility
to OCD.
Key Words
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Article info
Publication history
Published online: September 20, 2007
Accepted:
June 14,
2007
Received in revised form:
May 18,
2007
Received:
February 16,
2007
Identification
Copyright
© 2008 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
