A haplotype of the DRD1 gene is associated with alcohol dependence.
BACKGROUND
The D1 dopamine receptor has been involved in a number of brain functions, including motor control, inattentive symptoms and reward and reinforcement mechanisms. Indeed, DRD1 antagonists may reduce cocaine-seeking behavior and the acquisition of cocaine-cue associations. The D1.1/r4532 marker of the DRD1 gene has been associated with a large set of phenotypes including addictive behaviors, but none with alcohol dependence per se.


METHODS
We analyzed a population of 134 patients with alcohol dependence, also assessing more homogeneous (severe) phenotypes, comparing this sample with a healthy control population, assessing two SNPs within the DRD1 gene in order to depict the role of DRD1 polymorphisms and haplotypes.


RESULTS
The T allele of the rs686 polymorphism within DRD1 gene was significantly more frequent in patients with alcohol dependence (p = 0.0008), with a larger excess for patients with severe dependence (p = 6 x 10(-6)), and even more for patients with severe complications such as withdrawal seizures (p = 7 x 10(-7)). A specific haplotype rs686*T-rs4532*G within the DRD1 gene was significantly more precisely associated with alcohol dependence in our sample (p = 5 x 10(-6)).


CONCLUSIONS
Even though chance finding cannot be ruled out, convergent evidence is given that the DRD1 gene is a susceptibility gene in alcohol dependence, regarding the fact that relying on more homogeneous phenotypes (i.e., more severe patients) and more informative genetic markers (i.e., haplotypes) reinforce the initial association.
Batel
P
P
INSERM U675, Faculty of Medicine Bichat (IFR02) (Paris 7), Paris, France. philippe.batel@bjn.aphp.fr
Houchi
H
H
Daoust
M
M
Ramoz
N
N
Naassila
M
M
Gorwood
P
P
D000328:Adult; D000368:Aged; D000437:Alcoholism / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage / Q000235:genetics*; D005819:Genetic Markers / Q000235:genetics; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics; D017447:Receptors, Dopamine D1 / Q000235:genetics*
D005819:Genetic Markers; D017447:Receptors, Dopamine D1