The tachykinin receptor 3 is associated with alcohol and cocaine dependence.
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 <or= 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.
Foroud
Tatiana
T
Indiana University School of Medicine, Indianapolis, Indiana 46202-3002, USA. tforoud@iupui.edu
Wetherill
Leah Flury
LF
Kramer
John
J
Tischfield
Jay A
JA
Nurnberger
John I
JI
Schuckit
Marc A
MA
Xuei
Xiaoling
X
Edenberg
Howard J
HJ
D000437:Alcoholism / Q000235:genetics*; D019970:Cocaine-Related Disorders / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D018042:Receptors, Neurokinin-3 / Q000235:genetics*
D018042:Receptors, Neurokinin-3