Susceptibility Locus in Neurokinin-1 Receptor Gene Associated with Alcohol Dependence

Seneviratne, Chamindi, Ait-Daoud, Nassima, Ma, Jennie Z., Chen, Guo-Bo, Johnson, Bankole A. and Li, Ming D. (2009) Susceptibility Locus in Neurokinin-1 Receptor Gene Associated with Alcohol Dependence. Neuropsychopharmacology, 34 11: 2442-2449. doi:10.1038/npp.2009.65


Author Seneviratne, Chamindi
Ait-Daoud, Nassima
Ma, Jennie Z.
Chen, Guo-Bo
Johnson, Bankole A.
Li, Ming D.
Title Susceptibility Locus in Neurokinin-1 Receptor Gene Associated with Alcohol Dependence
Journal name Neuropsychopharmacology   Check publisher's open access policy
ISSN 0893-133X
1740-634X
Publication date 2009-01-01
Year available 2009
Sub-type Article (original research)
DOI 10.1038/npp.2009.65
Open Access Status Not Open Access
Volume 34
Issue 11
Start page 2442
End page 2449
Total pages 8
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Language eng
Formatted abstract
Substance P (SP), a neurotransmitter in stress pathways, exerts its effects mainly through the neurokinin-1 receptor (NK1R). Genetic and pharmacological studies show that binding of ligands to NK1R decreases anxiety-related behaviors, and therefore, self-administration of alcohol in mice and craving for alcohol in humans. As genetic variants may result in differential expression of the receptor through various molecular mechanisms, we examined whether allelic variations in the NK1R gene are associated with alcohol dependence (AD) by genotyping 11 single-nucleotide polymorphisms (SNPs) across NK1R in alcoholic (n=271) and healthy control (n=337) articipants of Caucasian descent. The AD was diagnosed using the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, fourth edition. Associations of the SNPs with AD were assessed at both the individual SNP and haplotype levels. We found that genotype and allele frequencies of rs6715729, a synonymous SNP in exon 1, differed significantly in alcoholics and in controls (p=0.0006; OR (odds ratio)=6.13; 95% CI4.06, 9.23). Haplotype analyses indicated two risk haplotypes for AD in the 5′ end of the gene, formed by the three-SNP combinations-rs6715729-rs735668-rs6741029. Taken together, we conclude that polymorphisms of NK1R are significantly associated with the development of AD in Caucasian individuals. Additional studies are needed to replicate these results in other samples and to elucidate the mechanism(s) by which these polymorphisms affect NK1R function in the brain.
Keyword Addiction
Alcohol Dependence
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ
Additional Notes For ERA

Document type: Journal Article
Sub-type: Article (original research)
Collection: Queensland Brain Institute Publications
 
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Created: Thu, 23 Oct 2014, 19:57:04 EST by Debra McMurtrie on behalf of Queensland Brain Institute