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  • Title: A haplotype of the DRD1 gene is associated with alcohol dependence.
    Author: Batel P, Houchi H, Daoust M, Ramoz N, Naassila M, Gorwood P.
    Journal: Alcohol Clin Exp Res; 2008 Apr; 32(4):567-72. PubMed ID: 18341651.
    Abstract:
    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.
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