Dopamine D4 receptor gene and severity of dependence

Family, twin and adoption studies demonstrate that substance dependence is determined partially by genes. Recent studies in opiate-dependent subjects have found a significant excess of the long-long (LL) allele of the 48bp repeat in the coding sequence of the DRD4 gene. This study examined this association further in a sample of 60 opiate dependent, 51 alcohol-dependent and 64 normal, healthy control subjects. No significant association between the polymorphism at DRD4 and opiate or alcohol abuse was found. However, results yielded a significant main effect on severity of dependence, demonstrating that individuals with the LL allele rated their severity of dependence significantly higher than those who had the short-short (SS) allele :[F(2, 101) = 5.0, p < 0.01]. This study suggests that the DRD4 gene does not directly influence vulnerability to substance dependence, but that possession of the LL genotype significantly increases severity of dependence.