A Haplotype of the DRD1 Gene Is Associated With Alcohol DependenceAlcoholism: Clinical and Experimental Research, Early Online, 13 Mar 2008
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.
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.
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 × 10−6), and even more for patients with severe complications such as withdrawal seizures (p = 7 × 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 × 10−6).
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.
Request Reprint E-Mail: philippe.batel@bjn.aphp.fr
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