PMID- 18534558
OWN - NLM
STAT- MEDLINE
DCOM- 20090408
LR  - 20221207
IS  - 1873-2402 (Electronic)
IS  - 0006-3223 (Print)
IS  - 0006-3223 (Linking)
VI  - 64
IP  - 11
DP  - 2008 Dec 1
TI  - Gene-gene interactions among CHRNA4, CHRNB2, BDNF, and NTRK2 in nicotine 
      dependence.
PG  - 951-7
LID - 10.1016/j.biopsych.2008.04.026 [doi]
AB  - BACKGROUND: Epidemiological data indicate that nicotine dependence (ND) are 
      influenced by genes, environmental factors, and their interactions. Although it 
      has been documented from molecular experiments that brain-derived neurotrophic 
      factor (BDNF) exerts its functions via neurotrophic tyrosine kinase receptor 2 
      (NTRK2) and both alpha 4 (CHRNA4) and beta 2 (CHRNB2) subunits are required to 
      form functional alpha 4 beta 2-containing nicotinic receptors (nAChRs), no study 
      is reported demonstrating that there exist gene-gene interactions among the four 
      genes in affecting ND. METHODS: To determine if gene-gene interactions exist 
      among the four genes, we genotyped six single nucleotide polymorphisms (SNPs) for 
      CHRNA4 and BDNF, nine SNPs for NTRK2, and four SNPs for CHRNB2 in a case-control 
      sample containing 275 unrelated smokers with a Fagerstrom Test for Nicotine 
      Dependence score of 4.0 or more and 348 unrelated nonsmokers. RESULTS: By using a 
      generalized multifactor dimensionality reduction algorithm recently developed by 
      us, we found highly significant gene-gene interactions for the gene pairs of 
      CHRNA4 and CHRNB2, CHRNA4 and NTRK2, CHRNB2 and NTRK2, and BDNF and NTRK2 (p < 
      .01 for all four gene pairs) and significant gene-gene interaction between CHRNA4 
      and BDNF (p = .031) on ND. No significant interaction was detected for CHRNB2 and 
      BDNF (p = .068). CONCLUSIONS: Our study provides first evidence on the presence 
      of gene-gene interaction among the four genes in affecting ND. Although CHRNB2 
      alone was not significantly associated with ND in several previously reported 
      association studies on ND, we found it affects ND through interactions with 
      CHRNA4 and NTRK2.
FAU - Li, Ming D
AU  - Li MD
AD  - Department of Psychiatry and Neurobehavioral Sciences, University of Virginia, 
      Charlottesville, Virginia 22911, USA. Ming_Li@virginia.edu
FAU - Lou, Xiang-Yang
AU  - Lou XY
FAU - Chen, Guobo
AU  - Chen G
FAU - Ma, Jennie Z
AU  - Ma JZ
FAU - Elston, Robert C
AU  - Elston RC
LA  - eng
GR  - R01 DA012844/DA/NIDA NIH HHS/United States
GR  - R01 DA012844-06A2/DA/NIDA NIH HHS/United States
GR  - DA-12844/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20080604
PL  - United States
TA  - Biol Psychiatry
JT  - Biological psychiatry
JID - 0213264
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Receptors, Nicotinic)
RN  - 0 (nicotinic acetylcholine receptor alpha4 subunit)
RN  - 0 (nicotinic receptor beta2)
RN  - EC 2.7.10.1 (Receptor, trkB)
SB  - IM
MH  - Adult
MH  - Black People/genetics
MH  - Brain-Derived Neurotrophic Factor/*genetics
MH  - Case-Control Studies
MH  - Epistasis, Genetic/*genetics
MH  - Female
MH  - Genetic Predisposition to Disease
MH  - Genotype
MH  - Humans
MH  - Linkage Disequilibrium
MH  - Male
MH  - Middle Aged
MH  - *Polymorphism, Single Nucleotide
MH  - Receptor, trkB/*genetics
MH  - Receptors, Nicotinic/*genetics
MH  - Retrospective Studies
MH  - Tobacco Use Disorder/*genetics
MH  - White People/genetics
MH  - Young Adult
PMC - PMC2592606
MID - NIHMS79409
EDAT- 2008/06/07 09:00
MHDA- 2009/04/09 09:00
PMCR- 2009/12/01
CRDT- 2008/06/07 09:00
PHST- 2008/03/04 00:00 [received]
PHST- 2008/04/22 00:00 [revised]
PHST- 2008/04/24 00:00 [accepted]
PHST- 2008/06/07 09:00 [pubmed]
PHST- 2009/04/09 09:00 [medline]
PHST- 2008/06/07 09:00 [entrez]
PHST- 2009/12/01 00:00 [pmc-release]
AID - S0006-3223(08)00504-0 [pii]
AID - 10.1016/j.biopsych.2008.04.026 [doi]
PST - ppublish
SO  - Biol Psychiatry. 2008 Dec 1;64(11):951-7. doi: 10.1016/j.biopsych.2008.04.026. 
      Epub 2008 Jun 4.