Reappraisal of the association between the DRD2 gene, alcoholism and addiction

We analysed the impact of the Taql Al allele of the D2 dopamine receptor ge ne on the risk for alcoholism, trying to depict three explanations frequent ly proposed to explain discrepancies in association and linkage studies: th at the Al allele may act as a marker rather than as a vulnerability factor, that stratification biases and unevaluated controls may explain positive r esults, and that the Al allele is modifying the phenotype rather than incre asing the risk for alcoholism. We thus tested another (dinucleotide STRP) m arker within the DRD2 gene. selected a new homogenous sample of 113 alcohol ic patients and 49 unaffected controls strictly matched for ethnic origins, and systematically assessed both samples with a semi-structured interview to detect (in both samples) alcohol dependence, but also such related trait s as specificities of complications. The frequency of the Al allele was not significantly different between alco holics and controls but when comparing different subgroups of alcoholics. t he Al allele was significantly more frequent in alcoholic patients with som atic complications (OR = 3.00, Cl[1.37-6.62]), social and professional comp lications (OR = 2.72, Cl[1.25-5.90]), or with co-morbid dependence (OR = 2. 88, 95% IC [1.16-7.15]). The association for co-morbid dependence and somat ic complications was also positive when taking into consideration both STRP and TaqlA polymorphisms. The Al allele does not increase the risk for alcoholism per se in our sampl e, but may be involved in a related trait which is partially dependent on t he diagnosis of alcoholism, through a disequilibrium with another close mut ation. (C) 2000 Editions scientifiques et medicales Elsevier SAS.