Influence of dopaminergic system gene polymorphisms on mixed amphetamine-type stimulants and opioid dependence in Malaysian Malays

Abstract

Background: The dopaminergic pathways have previously been reported to be involved in drug dependence. The candidate gene involved in the dopaminergic function has been associated with substance abuse. Objective: The objective of the study is to investigate the possible association between dopaminergic system gene polymorphisms with mixed amphetamine-type stimulants and opioid dependence in Malaysian Malays. The study has never been done anywhere else, due to its unique population of study subjects. Subjects and methods In this study, genetic polymorphisms of dopamine D2 receptor (DRD2) dopamine transporter (SLC6A3), dopamine beta-hydroxylase (DβH), and norepinephrine transporter (SLC6A2) in Malay males (n = 70) having mixed amphetamine-type stimulant (ATS) and opioid dependence were compared with those in control subjects (n = 87). DNA was extracted from leucocytes followed by single nucleotide polymorphism (SNP) determination using PCR-RFLP. The association of the gene with drug dependency was analyzed using chi-squared tests. Results: There was a significant difference between the genotype (χ 2 = 10.048, p < 0.01) and allele frequency (χ 2 = 14.039, p = 0.000) of the DRD2 rs1800497 gene in the drug dependence group as compared to the control. There was also a significant difference in DβH rs1611115 at the allelic (χ 2 = 4.483, p = 0.034) but not at genotypic levels (χ 2 = 7.572, p = 0.23) in both control and drug dependence groups. There was an association for SLC6A3 rs27072 with drug dependence at the genotypic level (χ 2 = 7.006, p = 0.030) although no significant difference exist at the allelic level (χ 2 = 2.091, p = 0.148). No significant difference was observed in SLC6A2 rs3785157 genes polymorphism at both genotype and allelic level in control and drug dependence group respectively (χ 2 = 0.94, p = 0.954) (χ 2 = 0.29, p = 0.865) indicating that these polymorphisms do not affect drug dependence. Conclusion: Our study suggests that DRD2 rs1800497, DβH rs1611115, and SLC6A3 rs27072 but not SLC6A2 rs3785157 are associated with drug-dependent behavior among Malaysian Malays.