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

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Abstract

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.

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Acknowledgements

We are thankful to the Social Awareness Service Organization (SASO), Imphal, and all the participants in the study.

Funding

The present study is supported by the Department of Biotechnology (DBT), Govt. of India grant to Reena Haobam and Usha Rajamma vide BT/251/NE/TBP/2011 dated 14.5.2012. Arunkumar Singh Koijam worked for this project as Junior Research Fellow.

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Authors and Affiliations

  1. Department of Biotechnology, Manipur University, Canchipur, Imphal, Manipur, 795003, India

    Arunkumar Singh Koijam, Aruna Chanu Hijam & Reena Haobam

  2. Department of Pathology, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS, USA

    Asem Surindro Singh

  3. Manovikas Biomedical Research & Diagnostic Centre, Manovikas Kendra, 482 Madudah, Plot I-24, Sector-J, EM Bypass, Kolkata, West Bengal, India

    Preeti Jaiswal, Kanchan Mukhopadhyay & Usha Rajamma

  4. Centre for Development & Aging Research, Inter University Centre for Biomedical Research & Super Speciality Hospital, MG University Campus, Thalappady, Rubber Board PO, Kottayam, Kerala, India

    Usha Rajamma

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  1. Arunkumar Singh Koijam
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  2. Aruna Chanu Hijam
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  3. Asem Surindro Singh
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  7. Reena Haobam
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Contributions

Reena Haobam, Usha Rajamma, and Kanchan Mukhopadhyay conceived, designed, and supervised the work; Arunkumar Singh Koijam performed research work; Aruna Chanu Hijam and Preeti Jaiswal assisted in research work; Arunkumar Singh Koijam and Asem Surindro Singh analysed data; Arunkumar Singh Koijam and Reena Haobam prepared the manuscript for publication. All the authors read and agreed to the manuscript.

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Correspondence to Reena Haobam.

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All procedures performed in the study were per the ethical standards of the Institutional Human Ethics Committee, Manipur University, and with the 1964 Helsinki declaration and its later amendments.

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Informed consent was obtained from all individual participants included in the study.

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Koijam, A.S., Hijam, A.C., Singh, A.S. et al. Association of Dopamine Transporter Gene with Heroin Dependence in an Indian Subpopulation from Manipur. J Mol Neurosci 71, 122–136 (2021). https://doi.org/10.1007/s12031-020-01633-5

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