Susceptibility Locus in Neurokinin-1 Receptor Gene Associated with Alcohol Dependence
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...
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Published in | Neuropsychopharmacology (New York, N.Y.) Vol. 34; no. 11; pp. 2442 - 2449 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
Cham
Springer International Publishing
01.10.2009
Nature Publishing Group |
Subjects | |
Online Access | Get full text |
ISSN | 0893-133X 1740-634X 1740-634X |
DOI | 10.1038/npp.2009.65 |
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Summary: | 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) participants 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% CI=4.06, 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. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 ObjectType-Article-2 ObjectType-Feature-1 content type line 23 |
ISSN: | 0893-133X 1740-634X 1740-634X |
DOI: | 10.1038/npp.2009.65 |