Association of DRD2 gene polymorphism with heroin dependence

Background: Dopamine receptors play a crucial role in the neuronal signalling of the mesolimbic system in the brain which regulates emotion, complex behaviour along with rewarding effects. The variants rs6276 of DRD2, 120bp indel of DRD2 and 12bp repeat have been reported to have effects on receptor activity. Aim: To analyse the genetic association of DRD2 and DRD2 genes with heroin dependence. Methods: Genetic association (based on alleles, genotypes and haplotypes) analyses for three variants of DRD2 and DRD2 genes were performed using UNPHASED version 3.1.5. in 290 participants (157 controls and 133 cases with heroin dependence) from Manipur, India. Interactions among the markers were also analysed using MDR 2.0 beta 8.4. Results: The post-hoc statistical power of the study was 0.683 (68.3%). Significantly higher distribution of AA genotype (p=0.005, OR=2.27, CI=1.21-4.27) of rs6276 (DRD2) was observed in cases with heroin dependence than in controls. Interestingly when analysis was made separately, genotypic association of rs6276 was observed in male subjects only (p=0.006, adjusted p=0.021) but not female subjects (p=0.103). G-S haplotype of rs6276-120bp indel (case frequency=0.214, control frequency=0.309, p=0.03) and S-L haplotype of 120bp indel-12bp repeat (case frequency=0.17, control frequency=0.25, p=0.02) were found to be significantly higher in controls than in cases. Conclusion: The study indicates evidences for genotypic association of rs6276 of DRD2 with heroin dependence. The 'AA' genotype of rs6276 in an individual is a possible risk factor for heroin dependence.