Association of Dopamine Transporter Gene with Heroin Dependence in an Indian Subpopulation from Manipur

• Published in: Journal of molecular neuroscience 2021, Vol.71 (1), p.122-136
• Main Authors: Koijam, Arunkumar Singh, Hijam, Aruna Chanu, Singh, Asem Surindro, Jaiswal, Preeti, Mukhopadhyay, Kanchan, Rajamma, Usha, Haobam, Reena
• Format: Article
• Language: English
• Subjects: Alleles; Biomedical and Life Sciences; Biomedicine; Cell Biology; Dependence; Dopamine; Dopamine receptors; Dopamine transporter; Gene polymorphism; Genetic analysis; Genotype & phenotype; Haplotypes; Heroin; Neurochemistry; Neurology; Neurosciences; Neurotransmission; Nucleotides; Polymorphism; Population genetics; Population studies; Proteomics; Reinforcement; Single-nucleotide polymorphism
• ISSN: 0895-8696; 1559-1166
• DOI: 10.1007/s12031-020-01633-5

Dopamine transporter (DAT) or solute carrier family 6 member 3 (SLC6A3) is a transmembrane protein regulating dopaminergic neurotransmission. It has been implicated in playing important roles in the dopaminergic reward pathways, and thus, DAT1 is a strong candidate gene for association studies with heroin dependence. A case-control study involving 279 individuals (147 controls and 132 heroin-dependent cases) was conducted. Ten polymorphisms of the DAT1 (SLC6A3) gene were analysed for its association with heroin dependence. Following the Hardy-Weinberg equilibrium (HWE) test, genetic association analyses were performed for the study groups. The post hoc statistical power of the study was 0.655 (65.5%). Single-nucleotide polymorphism (SNP) rs246997 was found to be significantly associated with heroin dependence at allelic, genotypic, and haplotypic levels. A significant difference in the distribution of 11R allele and 10R/11R genotype of rs28363170 between heroin-dependent cases and controls was also observed. Nominal significance at degrees of freedom (df) = 5 was also observed for rs28363170. Five bimarker-based haplotype combinations were also found to be associated with heroin dependence. For the first time, 13R allele (7R/13R genotype) and 14R allele (7R/14R genotype) were identified for rs3836790 in the population. The study also reports that the 11R allele and 10R/11R genotype of rs28363170 is associated with protection against heroin dependence. 7R and 6R alleles were also found to be the common alleles of rs3836790 in the study population. The study provides evidence for the association of polymorphisms of DAT1 (SLC6A3) with heroin dependence.