Abstract
BackgroundConflicting associations with heroin dependence have been found involving the A1 allele of dopamine D2 receptor gene (DRD2) TaqI A polymorphism.MethodsWe compared two samples of unrelated Spanish individuals, all of European origin: 281 methadone-maintained heroin-dependent patients (207 males and 74 females) who frequently used non-opioid substances, and 145 control subjects (98 males and 47 females).ResultsThe A1-A1 genotype was detected in 7.1% of patients and 1.4% of controls (P = 0.011, odds ratio = 5.48, 95% CI 1.26–23.78). Although the A1 allele was not associated with heroin dependence in the entire sample, the frequency of A1 allele was higher in male patients than in male controls (24.4% vs. 16.3%, P = 0.024, odds ratio = 1.65, 95% CI 1.07–2.57). A logistic regression analysis showed an interaction between DRD2 alleles and gender (odds ratio = 1.77, 95% CI 1.15–2.70).ConclusionOur results indicate that, in Spanish individuals, genotypes of the DRD2 TaqI A polymorphism contribute to variations in the risk of heroin dependence, while single alleles contribute only in males.
Highlights
Conflicting associations with heroin dependence have been found involving the A1 allele of dopamine D2 receptor gene (DRD2) TaqI A polymorphism
Both features could maximise a study's ability to detect genetic associations: with non-opioid substance use, because it is related with the dopamine receptor D2 (DRD2) A1 allele [16]; and with methadone treatment, because it can be a marker of heroin dependence severity [25]
A1 or A2 could have been associated with heroin use), while we found that the associated allele was A1, just as in previous reports; 3) The male-limited association of A1 allele with heroin dependence must be considered as a preliminary finding, because more males than females participated in the present study and there is no indication of gender dimorphism in regard with the TaqI A alleles in the literature; 4) The findings of the present study may not be generalizable, because all study participants belonged to the same population
Summary
Conflicting associations with heroin dependence have been found involving the A1 allele of dopamine D2 receptor gene (DRD2) TaqI A polymorphism. Genes that could be risk factors for heroin dependence have not been consistently identified; genetic epidemiology studies have shown that they do have an impact. The gene coding for the dopamine receptor D2 (DRD2) could be involved in heroin dependence and other SUD as a nonspecific genetic factor, because opioids and other substances of abuse induce some of their rewarding effects through the mesolimbic dopamine system [5,6]. An absence of opioid-rewarding effects has been reported in mice lacking DRD2 [7]
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