PMID- 18518926
OWN - NLM
STAT- MEDLINE
DCOM- 20090410
LR  - 20211028
IS  - 1601-183X (Electronic)
IS  - 1601-183X (Linking)
VI  - 7
IP  - 7
DP  - 2008 Oct
TI  - Additive effect of BDNF and REST polymorphisms is associated with improved 
      general cognitive ability.
PG  - 714-9
LID - 10.1111/j.1601-183X.2008.00409.x [doi]
AB  - Brain-derived neurotrophic factor (BDNF) is a pleiotropic protein involved in 
      neuronal proliferation, differentiation, synaptic plasticity and survival. 
      Independent studies investigating association between the functional BDNF 
      Val66Met polymorphism and cognitive abilities have reported some conflicting 
      findings, which may reflect inadequate sample size, variation in testing methods, 
      population stratification or the confounding effects of other genes. To test the 
      latter hypothesis, we screened and genotyped polymorphisms in the RE1-silencing 
      transcription factor (REST) gene whose function includes the downregulation of 
      BDNF expression. We identified an exon 4 hexadecapeptide variable number tandem 
      repeat (VNTR) with either four or five copies that was located within a 
      proline-rich domain and investigated a further five single nucleotide 
      polymorphisms (SNPs). Using a cohort of 746 community-dwelling older volunteers, 
      we analysed REST genotype data both independently and in combination with the 
      BDNF Val66Met polymorphism. A haplotype within the REST gene containing the four 
      copy VNTR and a non-synonymous SNP showed a weak but significant association with 
      a higher score of general intelligence (P = 0.05). Analysis of this haplotype and 
      the BDNF Val66Met polymorphism in combination showed a significant interaction 
      (global P-value = 0.0003) with an additive increase in cognitive performance for 
      those possessing the BDNF Val66 allele and the REST haplotype containing the four 
      copy repeat (P = 0.004). The REST haplotypes in combination with the BDNF Met66 
      polymorphism did not reduce cognitive performance more than the independent 
      influence of the Met66 allele. Our results suggest that investigation of a common 
      REST polymorphism may be necessary to help reduce contrasting reports based 
      around BDNF Val66Met and cognition.
FAU - Miyajima, F
AU  - Miyajima F
AD  - Centre for Integrated Genomic Medical Research, School of Medicine, The 
      University of Manchester, Manchester, UK.
FAU - Quinn, J P
AU  - Quinn JP
FAU - Horan, M
AU  - Horan M
FAU - Pickles, A
AU  - Pickles A
FAU - Ollier, W E
AU  - Ollier WE
FAU - Pendleton, N
AU  - Pendleton N
FAU - Payton, A
AU  - Payton A
LA  - eng
GR  - G0701003/MRC_/Medical Research Council/United Kingdom
GR  - BB_/Biotechnology and Biological Sciences Research Council/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080602
PL  - England
TA  - Genes Brain Behav
JT  - Genes, brain, and behavior
JID - 101129617
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (RE1-silencing transcription factor)
RN  - 0 (Repressor Proteins)
RN  - 9007-49-2 (DNA)
SB  - IM
MH  - Aged
MH  - Aged, 80 and over
MH  - Alleles
MH  - Base Sequence
MH  - Brain-Derived Neurotrophic Factor/*genetics
MH  - Cognition/*physiology
MH  - Cross-Sectional Studies
MH  - DNA/genetics
MH  - Female
MH  - Genotype
MH  - Haplotypes
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Molecular Sequence Data
MH  - Neuropsychological Tests
MH  - Polymorphism, Genetic/*genetics
MH  - Repressor Proteins/*genetics
MH  - Reverse Transcriptase Polymerase Chain Reaction
EDAT- 2008/06/04 09:00
MHDA- 2009/04/11 09:00
CRDT- 2008/06/04 09:00
PHST- 2008/06/04 09:00 [pubmed]
PHST- 2009/04/11 09:00 [medline]
PHST- 2008/06/04 09:00 [entrez]
AID - GBB409 [pii]
AID - 10.1111/j.1601-183X.2008.00409.x [doi]
PST - ppublish
SO  - Genes Brain Behav. 2008 Oct;7(7):714-9. doi: 10.1111/j.1601-183X.2008.00409.x. 
      Epub 2008 Jun 2.