PMID- 16568151
OWN - NLM
STAT- MEDLINE
DCOM- 20061031
LR  - 20220227
IS  - 1359-4184 (Print)
IS  - 1359-4184 (Linking)
VI  - 11
IP  - 7
DP  - 2006 Jul
TI  - A complex polymorphic region in the brain-derived neurotrophic factor (BDNF) gene 
      confers susceptibility to bipolar disorder and affects transcriptional activity.
PG  - 695-703
AB  - Previous studies have suggested that genetic variations in the brain-derived 
      neurotrophic factor (BDNF) gene may be associated with several neuropsychiatric 
      diseases including bipolar disorder. The present study examined a microsatellite 
      polymorphism located approximately 1.0 kb upstream of the translation initiation 
      site of the BDNF gene for novel sequence variations, association with bipolar 
      disorder, and effects on transcriptional activity. Detailed sequencing analysis 
      revealed that this polymorphism is not a simple dinucleotide repeat, but it is 
      highly polymorphic with a complex structure containing three types of 
      dinucleotide repeats, insertion/deletion, and nucleotide substitutions that gives 
      rise to a total of 23 novel allelic variants. We obtained evidence supporting the 
      association between this polymorphic region (designated as BDNF-linked complex 
      polymorphic region (BDNF-LCPR)) and bipolar disorder. One of the major alleles 
      ('A1' allele) was significantly more common in patients than in controls (odds 
      ratio 2.8, 95% confidential interval 1.5-5.3, P=0.001). Furthermore, a luciferase 
      reporter gene assay in rat primary cultured neurons suggests that this risk 
      allele (A1) has a lower-transcription activity, compared to the other alleles. 
      Our results suggest that the BDNF-LCPR is a functional variation that confers 
      susceptibility to bipolar disorder and affects transcriptional activity of the 
      BDNF gene.
FAU - Okada, T
AU  - Okada T
AD  - Department of Mental Disorder Research, National Institute of Neuroscience, 
      National Center of Neurology and Psychiatry, Tokyo, Japan.
FAU - Hashimoto, R
AU  - Hashimoto R
FAU - Numakawa, T
AU  - Numakawa T
FAU - Iijima, Y
AU  - Iijima Y
FAU - Kosuga, A
AU  - Kosuga A
FAU - Tatsumi, M
AU  - Tatsumi M
FAU - Kamijima, K
AU  - Kamijima K
FAU - Kato, T
AU  - Kato T
FAU - Kunugi, H
AU  - Kunugi H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20060328
PL  - England
TA  - Mol Psychiatry
JT  - Molecular psychiatry
JID - 9607835
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Recombinant Fusion Proteins)
SB  - IM
MH  - Adult
MH  - Alleles
MH  - Amino Acid Substitution
MH  - Animals
MH  - Base Sequence
MH  - Bipolar Disorder/*genetics
MH  - Brain-Derived Neurotrophic Factor/*genetics/physiology
MH  - Case-Control Studies
MH  - Cells, Cultured/metabolism
MH  - *Dinucleotide Repeats
MH  - Female
MH  - Gene Frequency
MH  - Genes, Reporter
MH  - Genetic Predisposition to Disease
MH  - Humans
MH  - Japan
MH  - Linkage Disequilibrium
MH  - Male
MH  - Middle Aged
MH  - Molecular Sequence Data
MH  - Mutation, Missense
MH  - Neurons/metabolism
MH  - Point Mutation
MH  - *Polymorphism, Genetic
MH  - Rats
MH  - Recombinant Fusion Proteins/biosynthesis
MH  - Transcription, Genetic/*genetics
EDAT- 2006/03/29 09:00
MHDA- 2006/11/01 09:00
CRDT- 2006/03/29 09:00
PHST- 2006/03/29 09:00 [pubmed]
PHST- 2006/11/01 09:00 [medline]
PHST- 2006/03/29 09:00 [entrez]
AID - 4001822 [pii]
AID - 10.1038/sj.mp.4001822 [doi]
PST - ppublish
SO  - Mol Psychiatry. 2006 Jul;11(7):695-703. doi: 10.1038/sj.mp.4001822. Epub 2006 Mar 
      28.