PMID- 17884018
OWN - NLM
STAT- MEDLINE
DCOM- 20080414
LR  - 20220309
IS  - 1873-2402 (Electronic)
IS  - 0006-3223 (Linking)
VI  - 63
IP  - 6
DP  - 2008 Mar 15
TI  - Extensive genotyping of the BDNF and NTRK2 genes define protective haplotypes 
      against obsessive-compulsive disorder.
PG  - 619-28
AB  - 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.
FAU - Alonso, Pino
AU  - Alonso P
AD  - OCD Clinical and Research Unit, Psychiatry Department, Hospital Universitari de 
      Bellvitge, Barcelona, Spain.
FAU - Gratacos, Monica
AU  - Gratacos M
FAU - Menchon, Jose M
AU  - Menchon JM
FAU - Saiz-Ruiz, Jeronimo
AU  - Saiz-Ruiz J
FAU - Segalas, Cinto
AU  - Segalas C
FAU - Baca-Garcia, Enrique
AU  - Baca-Garcia E
FAU - Labad, Javier
AU  - Labad J
FAU - Fernandez-Piqueras, Jose
AU  - Fernandez-Piqueras J
FAU - Real, Eva
AU  - Real E
FAU - Vaquero, Concepcion
AU  - Vaquero C
FAU - Perez, Mercedes
AU  - Perez M
FAU - Dolengevich, Helen
AU  - Dolengevich H
FAU - Gonzalez, Juan R
AU  - Gonzalez JR
FAU - Bayes, Monica
AU  - Bayes M
FAU - de Cid, Rafael
AU  - de Cid R
FAU - Vallejo, Julio
AU  - Vallejo J
FAU - Estivill, Xavier
AU  - Estivill X
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070919
PL  - United States
TA  - Biol Psychiatry
JT  - Biological psychiatry
JID - 0213264
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - EC 2.7.10.1 (Receptor, trkB)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Brain-Derived Neurotrophic Factor/*genetics
MH  - Case-Control Studies
MH  - Female
MH  - Genetic Predisposition to Disease/*genetics/psychology
MH  - *Genotype
MH  - Haplotypes/*genetics
MH  - Humans
MH  - Linkage Disequilibrium
MH  - Male
MH  - Middle Aged
MH  - Obsessive-Compulsive Disorder/diagnosis/*genetics/psychology
MH  - Phenotype
MH  - Polymorphism, Single Nucleotide/genetics
MH  - Receptor, trkB/*genetics
EDAT- 2007/09/22 09:00
MHDA- 2008/04/15 09:00
CRDT- 2007/09/22 09:00
PHST- 2007/02/16 00:00 [received]
PHST- 2007/05/18 00:00 [revised]
PHST- 2007/06/14 00:00 [accepted]
PHST- 2007/09/22 09:00 [pubmed]
PHST- 2008/04/15 09:00 [medline]
PHST- 2007/09/22 09:00 [entrez]
AID - S0006-3223(07)00608-7 [pii]
AID - 10.1016/j.biopsych.2007.06.020 [doi]
PST - ppublish
SO  - Biol Psychiatry. 2008 Mar 15;63(6):619-28. doi: 10.1016/j.biopsych.2007.06.020. 
      Epub 2007 Sep 19.