Understanding the influences of genes involved in dopamine and serotonin metabolism, such as the aldehyde dehydrogenase 2 (ALDH2) and alcohol dehydrogenase 1B (ADH1B) genes, is critical for understanding addictive behavior. In addition, dopamine D2 receptor (DRD2) gene may also interact with the dopamine metabolizing genes and link to addiction. Therefore, we investigated the association between the ALDH2, ADH1B and DRD2 polymorphisms and heroin dependence. Heroin-dependent Han Chinese patients (n=304) and healthy controls (n=335) were recruited. Genotypes of ALDH2, ADH1B and DRD2 polymorphisms were analyzed using a polymerase chain reaction with restriction fragment length polymorphism. The frequency of the ALDH2*1/*1 genotype was significantly lower in heroin-dependent patients than in controls, but the frequency of ADH1B and DRD2 genotypes was not significantly different. Further stratification of the ALDH2 gene with the ADH1B gene showed that the protective effect of ALDH2*1/*1 existed only in patients who also carried the ADH1B*1/*1 and ADH1B*1/*2 genotype. Logistic regression analysis showed a significant interaction between ALDH2 and ADH1B (P=0.022) and DRD2, ALDH2 and ADH1B in patients (P=0.037). The ALDH2*1/*1, ADH1B*1/*1, and ADH1B*1/*2 genotypes may interact and protect their carriers against heroin dependence and the protective effect may be varied by the DRD2 gene polymorphism. We conclude that the protective effect of the ALDH2 polymorphism against heroin dependence may be modified by the ADH1B and DRD2 polymorphism.
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