PMID- 17460549
OWN - NLM
STAT- MEDLINE
DCOM- 20070518
LR  - 20220309
IS  - 1744-6872 (Print)
IS  - 1744-6872 (Linking)
VI  - 17
IP  - 3
DP  - 2007 Mar
TI  - A splice site polymorphism in the G-protein beta subunit influences 
      antidepressant efficacy in depression.
PG  - 207-15
AB  - OBJECTIVE: Recent evidence suggests that signalling cascades located downstream 
      of monoamine receptors are altered following antidepressant treatment. Our 
      objective was to investigate whether genetic polymorphisms in genes involved in 
      these signalling cascades influenced antidepressant efficacy. METHODS: 
      Polymorphisms in the G-protein beta subunit GNB3, the cAMP response element 
      binding protein 1 gene (CREB1), the brain derived neurotrophic factor (BDNF) and 
      CREB binding protein (CREBBP) were studied in well characterised unipolar (n=166) 
      and early onset (n=102) depressive populations and correlated with treatment 
      response. RESULTS: The GNB3 C825T polymorphism, which results in a 41 amino acid 
      deletion, was significantly associated with lack of remission (OR=0.18, P=0.02) 
      and lack of response (OR=0.26, P=0.03) following 2nd switch treatment. A cytosine 
      deletion 16 base pairs from the start of exon 8 in CREB1 was found more 
      frequently in remitters and responders to 2nd switch antidepressant drug therapy, 
      although these differences failed to reach significance. Polymorphisms detected 
      BDNF (G196A) and CREBBP (T651 C) did not appear to influence antidepressant 
      response. CONCLUSIONS: These results suggest that inheritance of the GNB3C825T 
      allele may significantly influence antidepressant response and emphasises the 
      potential importance of polymorphisms in genes in signalling cascades activated 
      by commonly prescribed antidepressants.
FAU - Wilkie, Murray J V
AU  - Wilkie MJ
AD  - Biomedical Research Centre, University of Dundee, Ninewells Hospital and Medical 
      School, Dundee, UK.
FAU - Smith, Daniel
AU  - Smith D
FAU - Reid, Ian C
AU  - Reid IC
FAU - Day, Richard K
AU  - Day RK
FAU - Matthews, Keith
AU  - Matthews K
FAU - Wolf, Charles Roland
AU  - Wolf CR
FAU - Blackwood, Douglas
AU  - Blackwood D
FAU - Smith, Gillian
AU  - Smith G
LA  - eng
GR  - G9810900/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Pharmacogenet Genomics
JT  - Pharmacogenetics and genomics
JID - 101231005
RN  - 0 (Antidepressive Agents)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (CREB1 protein, human)
RN  - 0 (Cyclic AMP Response Element-Binding Protein)
RN  - 0 (G-protein beta3 subunit)
RN  - 0 (GTP-Binding Protein beta Subunits)
RN  - 0 (RNA Splice Sites)
RN  - EC 2.3.1.48 (CREB-Binding Protein)
RN  - EC 2.3.1.48 (CREBBP protein, human)
RN  - EC 3.6.5.1 (Heterotrimeric GTP-Binding Proteins)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Antidepressive Agents/*therapeutic use
MH  - Brain-Derived Neurotrophic Factor/genetics
MH  - CREB-Binding Protein/genetics
MH  - Cyclic AMP Response Element-Binding Protein/genetics
MH  - Depression/*drug therapy/*genetics
MH  - Female
MH  - GTP-Binding Protein beta Subunits/*genetics
MH  - Genotype
MH  - Heterotrimeric GTP-Binding Proteins/genetics
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - *Polymorphism, Genetic
MH  - RNA Splice Sites/*genetics
MH  - Treatment Outcome
EDAT- 2007/04/27 09:00
MHDA- 2007/05/19 09:00
CRDT- 2007/04/27 09:00
PHST- 2007/04/27 09:00 [pubmed]
PHST- 2007/05/19 09:00 [medline]
PHST- 2007/04/27 09:00 [entrez]
AID - 01213011-200703000-00005 [pii]
AID - 10.1097/FPC.0b013e32801a3be6 [doi]
PST - ppublish
SO  - Pharmacogenet Genomics. 2007 Mar;17(3):207-15. doi: 10.1097/FPC.0b013e32801a3be6.