Document Detail


Nominal association with CHRNA4 variants and nicotine dependence.
MedLine Citation:
PMID:  23350800     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Nicotine binds to nicotinic acetylcholine receptors and studies in animal models have shown that α4β2 receptors mediate many behavioral effects of nicotine. Human genetics studies have provided support that variation in the gene that codes for the α4 subunit influences nicotine dependence (ND), but the evidence for the involvement of the β2 subunit gene is less convincing. In this study, we examined the genetic association between variation in the genes that code for the α4 (CHRNA4) and β2 (CHRNB2) subunits of the nicotinic acetylcholine receptor and a quantitative measure of lifetime DSM-IV ND symptom counts. We performed this analysis in two longitudinal family-based studies focused on adolescent antisocial drug abuse: the Center on Antisocial Drug Dependence (CADD, N = 313 families) and Genetics of Antisocial Drug Dependence (GADD, N = 111 families). Family-based association tests were used to examine associations between 14 single nucleotide polymorphisms (SNPs) in CHRNA4 and CHRNB2 and ND symptoms. Symptom counts were corrected for age, sex and clinical status prior to the association analysis. Results, when the samples were combined, provided modest evidence that SNPs in CHRNA4 are associated with ND. The minor allele at both rs1044394 (A; Z = 1.988, P = 0.047, unadjusted P-value) and rs1044396 (G; Z = 2.398, P = 0.017, unadjusted P-value) was associated with increased risk of ND symptoms. These data provide suggestive evidence that variation in the α4 subunit of the nicotinic acetylcholine receptor may influence ND liability.
Authors:
H M Kamens; R P Corley; M B McQueen; M C Stallings; C J Hopfer; T J Crowley; S A Brown; J K Hewitt; M A Ehringer
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2013-02-06
Journal Detail:
Title:  Genes, brain, and behavior     Volume:  12     ISSN:  1601-183X     ISO Abbreviation:  Genes Brain Behav.     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-04-04     Completed Date:  2013-09-23     Revised Date:  2014-04-01    
Medline Journal Info:
Nlm Unique ID:  101129617     Medline TA:  Genes Brain Behav     Country:  England    
Other Details:
Languages:  eng     Pagination:  297-304     Citation Subset:  IM    
Copyright Information:
Genes, Brain and Behavior © 2013 Blackwell Publishing Ltd and International Behavioural and Neural Genetics Society.
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Adult
Alleles
Diagnostic and Statistical Manual of Mental Disorders
Female
Genetic Association Studies
Humans
Longitudinal Studies
Male
Pedigree
Polymorphism, Single Nucleotide*
Receptors, Nicotinic / genetics*
Tobacco Use Disorder / diagnosis,  genetics*
Grant Support
ID/Acronym/Agency:
K01 AA019447/AA/NIAAA NIH HHS; K01AA019447/AA/NIAAA NIH HHS; P60 DA011015/DA/NIDA NIH HHS; P60 DA011015/DA/NIDA NIH HHS; R01 AA017889/AA/NIAAA NIH HHS; R01 AA017889/AA/NIAAA NIH HHS; R01 DA012845/DA/NIDA NIH HHS; R01 DA012845/DA/NIDA NIH HHS; R01 DA021905/DA/NIDA NIH HHS; R01 DA021905/DA/NIDA NIH HHS; R01 DA021913/DA/NIDA NIH HHS; R01 DA021913/DA/NIDA NIH HHS
Chemical
Reg. No./Substance:
0/Receptors, Nicotinic; 0/nicotinic acetylcholine receptor alpha4 subunit; 0/nicotinic receptor beta2
Comments/Corrections

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