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Association of Dopamine Transporter Gene with Heroin Dependence in an Indian Subpopulation from Manipur.
Journal of Molecular Neuroscience ( IF 2.8 ) Pub Date : 2020-06-18 , DOI: 10.1007/s12031-020-01633-5
Arunkumar Singh Koijam 1 , Aruna Chanu Hijam 1 , Asem Surindro Singh 2 , Preeti Jaiswal 3 , Kanchan Mukhopadhyay 3 , Usha Rajamma 3, 4 , Reena Haobam 1
Affiliation  

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.



中文翻译:

多巴胺转运蛋白基因与曼尼普尔印度亚群海洛因依赖的关联。

多巴胺转运蛋白 (DAT) 或溶质载体家族 6 成员 3 (SLC6A3) 是一种跨膜蛋白,可调节多巴胺能神经传递。它在多巴胺能奖赏通路中发挥重要作用,因此,DAT1是与海洛因依赖相关联研究的有力候选基因。进行了一项涉及 279 人(147 名对照者和 132 名海洛因依赖者)的病例对照研究。DAT1 (SLC6A3) 的十个多态性分析了基因与海洛因依赖的关联。在 Hardy-Weinberg 平衡 (HWE) 测试之后,对研究组进行了遗传关联分析。该研究的事后统计功效为 0.655 (65.5%)。发现单核苷酸多态性 (SNP) rs246997 在等位基因、基因型和单倍型水平上与海洛因依赖显着相关。还观察到海洛因依赖病例和对照之间 11R 等位基因和 rs28363170 的 10R/11R 基因型分布的显着差异。对于 rs28363170,还观察到自由度 (df) = 5 的名义显着性。还发现五种基于双标记的单倍型组合与海洛因依赖有关。首次,在人群中鉴定出 rs3836790 的 13R 等位基因(7R/13R 基因型)和 14R 等位基因(7R/14R 基因型)。该研究还报告说,rs28363170 的 11R 等位基因和 10R/11R 基因型与防止海洛因依赖有关。7R 和 6R 等位基因也被发现是研究人群中 rs3836790 的常见等位基因。该研究为多态性的关联提供了证据DAT1 (SLC6A3)海洛因依赖。

更新日期:2020-06-18
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