The tachykinin receptor 3 is associated with alcohol and cocaine dependence

Tatiana Foroud, Leah Flury Wetherill, John Kramer, Jay A. Tischfield, John Nurnberger, Marc A. Schuckit, Xiaoling Xuei, Howard Edenberg

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Background: A broad region on chromosome 4q was previously linked to the phenotype of alcohol dependence in the Collaborative Study on the Genetics of Alcoholism sample. A strong positional candidate gene was identified within this region: tachykinin receptor 3 gene (TACR3), which encodes tachykinin receptor 3 (NK3R), the receptor for the tachykinin 3 (neurokinin B) peptide. Pharmacological studies have provided evidence that the administration of NK3R agonists attenuates the intake of alcohol and NK3R can also mediate the acute and chronic behavioral effects of cocaine. Methods: Thirty SNPs were genotyped throughout TACR3. Family based association analysis was performed in 219 European American families to detect an association with alcohol dependence. Subsequent analyses were performed to evaluate the evidence of association with other definitions of alcohol dependence as well as cocaine dependence. Results: Seven of the 9 SNPs in the 3′ region of TACR3 provided significant evidence of association with alcohol dependence (p ≤ 0.05). Further analyses suggest that the evidence of association is strongest among those subjects with more severe alcohol dependence (defined by ICD-10) and those with co-morbid cocaine dependence. Haplotype analyses further strengthen the evidence of association in the 3′ region of the gene. Conclusions: These results indicate that sequence variations in TACR3 contribute to the variation in more severe alcohol dependent individuals and those who are also cocaine dependent.

Original languageEnglish
Pages (from-to)1023-1030
Number of pages8
JournalAlcoholism: Clinical and Experimental Research
Volume32
Issue number6
DOIs
StatePublished - Jun 2008

Fingerprint

Tachykinin Receptors
Cocaine-Related Disorders
Cocaine
Alcoholism
Alcohols
Genes
Single Nucleotide Polymorphism
Neurokinin B
International Classification of Diseases
Haplotypes
Chromosomes
Pharmacology
Phenotype
Peptides

Keywords

  • Alcoholism
  • Association
  • Family Study
  • SNP
  • Tachykinin Receptor 3 Gene

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Toxicology

Cite this

The tachykinin receptor 3 is associated with alcohol and cocaine dependence. / Foroud, Tatiana; Wetherill, Leah Flury; Kramer, John; Tischfield, Jay A.; Nurnberger, John; Schuckit, Marc A.; Xuei, Xiaoling; Edenberg, Howard.

In: Alcoholism: Clinical and Experimental Research, Vol. 32, No. 6, 06.2008, p. 1023-1030.

Research output: Contribution to journalArticle

Foroud, Tatiana ; Wetherill, Leah Flury ; Kramer, John ; Tischfield, Jay A. ; Nurnberger, John ; Schuckit, Marc A. ; Xuei, Xiaoling ; Edenberg, Howard. / The tachykinin receptor 3 is associated with alcohol and cocaine dependence. In: Alcoholism: Clinical and Experimental Research. 2008 ; Vol. 32, No. 6. pp. 1023-1030.
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