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本文引用的文献

1
Dopamine transporter DAT and receptor DRD2 variants affect risk of lethal cocaine abuse: a gene-gene-environment interaction.多巴胺转运体 DAT 和多巴胺受体 DRD2 变体影响致命可卡因滥用的风险:基因-基因-环境相互作用。
Transl Psychiatry. 2013 Jan 22;3(1):e222. doi: 10.1038/tp.2012.146.
2
Rs1076560, a functional variant of the dopamine D2 receptor gene, confers risk of schizophrenia in Han Chinese.多巴胺 D2 受体基因的功能性变异体 Rs1076560 可增加汉族人群患精神分裂症的风险。
Neurosci Lett. 2012 Jun 14;518(1):41-4. doi: 10.1016/j.neulet.2012.04.052. Epub 2012 Apr 30.
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Deficits in dopamine D(2) receptors and presynaptic dopamine in heroin dependence: commonalities and differences with other types of addiction.海洛因成瘾中多巴胺 D(2)受体和多巴胺前体的缺失:与其他成瘾类型的异同。
Biol Psychiatry. 2012 Feb 1;71(3):192-8. doi: 10.1016/j.biopsych.2011.08.024. Epub 2011 Oct 19.
4
DRD2 genotype-based variation of default mode network activity and of its relationship with striatal DAT binding.DRD2 基因型对默认模式网络活动及其与纹状体 DAT 结合的影响。
Schizophr Bull. 2013 Jan;39(1):206-16. doi: 10.1093/schbul/sbr128. Epub 2011 Oct 5.
5
Resting posterior minus frontal EEG slow oscillations is associated with extraversion and DRD2 genotype.静息后额部 EEG 慢波与外向性和 DRD2 基因型有关。
Biol Psychol. 2011 Jul;87(3):407-13. doi: 10.1016/j.biopsycho.2011.05.006. Epub 2011 Jun 7.
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DRD2/AKT1 interaction on D2 c-AMP independent signaling, attentional processing, and response to olanzapine treatment in schizophrenia.DRD2/AKT1 相互作用于 D2 c-AMP 非依赖性信号转导、注意加工以及精神分裂症的奥氮平治疗反应。
Proc Natl Acad Sci U S A. 2011 Jan 18;108(3):1158-63. doi: 10.1073/pnas.1013535108. Epub 2010 Dec 27.
7
Intronic polymorphisms affecting alternative splicing of human dopamine D2 receptor are associated with cocaine abuse.内含子多态性影响人类多巴胺 D2 受体的可变剪接,与可卡因滥用有关。
Neuropsychopharmacology. 2011 Mar;36(4):753-62. doi: 10.1038/npp.2010.208. Epub 2010 Dec 8.
8
D2 receptor genotype and striatal dopamine signaling predict motor cortical activity and behavior in humans.D2 受体基因型和纹状体多巴胺信号预测人类运动皮层活动和行为。
Neuroimage. 2011 Feb 14;54(4):2915-21. doi: 10.1016/j.neuroimage.2010.11.034. Epub 2010 Nov 16.
9
Genetically determined measures of striatal D2 signaling predict prefrontal activity during working memory performance.遗传决定的纹状体 D2 信号测量可预测工作记忆表现期间前额叶活动。
PLoS One. 2010 Feb 22;5(2):e9348. doi: 10.1371/journal.pone.0009348.
10
Association analysis between polymorphisms in the dopamine D2 receptor (DRD2) and dopamine transporter (DAT1) genes with cocaine dependence.多巴胺 D2 受体 (DRD2) 和多巴胺转运体 (DAT1) 基因多态性与可卡因依赖的关联分析。
Neurosci Lett. 2010 Apr 5;473(2):87-91. doi: 10.1016/j.neulet.2010.02.021. Epub 2010 Feb 17.

多巴胺受体D2(DRD2)单核苷酸多态性rs1076560与阿片类药物成瘾有关。

The dopamine receptor D2 (DRD2) SNP rs1076560 is associated with opioid addiction.

作者信息

Clarke Toni-Kim, Weiss Amy R D, Ferarro Thomas N, Kampman Kyle M, Dackis Charles A, Pettinati Helen M, O'brien Charles P, Oslin David W, Lohoff Falk W, Berrettini Wade H

机构信息

Center for Neurobiology and Behavior, Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, PA, 19104, USA.

出版信息

Ann Hum Genet. 2014 Jan;78(1):33-9. doi: 10.1111/ahg.12046. Epub 2013 Nov 25.

DOI:10.1111/ahg.12046
PMID:24359476
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4013426/
Abstract

The risk for drug addiction is partially heritable. Genes of the dopamine system are likely candidates to harbour risk variants, as dopamine neurotransmission is involved in mediating the rewarding effects of drugs of abuse. One functional single nucleotide polymorphism in dopamine receptor D2 (DRD2), rs1076560, is involved in regulating splicing of the gene and alters the ratio of DRD2 isoforms located pre- and postsynaptically. rs1076560 has been previously associated with cocaine abuse and we set out to confirm this association in a sample of European American (EA) (n = 336) and African American (AA) (n = 1034) cocaine addicts and EA (n = 656) and AA (n = 668) controls. We also analysed the role of rs1076560 in opioid dependence by genotyping EA (n = 1041) and AA (n = 284) opioid addicts. rs1076560 was found to be nominally associated with opioid dependence in EAs (p = 0.02, OR = 1.27) and AAs (p = 0.03, OR = 1.43). When both opioid-addicted ancestral samples were combined, rs1076560 was significantly associated with increased risk for drug dependence (p = 0.0038, OR = 1.29). This association remained significant after correction for multiple testing. No association was found with cocaine dependence. These data demonstrate the importance of dopamine gene variants in the risk for opioid dependence and highlight a functional polymorphism that warrants further study.

摘要

药物成瘾风险具有部分遗传性。多巴胺系统的基因很可能携带着风险变异,因为多巴胺神经传递参与介导滥用药物的奖赏效应。多巴胺受体D2(DRD2)中的一个功能性单核苷酸多态性rs1076560,参与调节该基因的剪接,并改变突触前和突触后DRD2亚型的比例。rs1076560先前已与可卡因滥用相关联,我们着手在一组欧美裔(EA)(n = 336)和非裔美国人(AA)(n = 1034)可卡因成瘾者以及EA(n = 656)和AA(n = 668)对照组中证实这种关联。我们还通过对EA(n = 1041)和AA(n = 284)阿片类成瘾者进行基因分型,分析了rs1076560在阿片类药物依赖中的作用。结果发现,rs1076560在欧美裔(p = 0.02,OR = 1.27)和非裔美国人(p = 0.03,OR = 1.43)中与阿片类药物依赖存在名义上的关联。当将两个阿片类成瘾的祖先样本合并时,rs1076560与药物依赖风险增加显著相关(p = 0.0038,OR = 1.29)。在进行多重检验校正后,这种关联仍然显著。未发现与可卡因依赖有关联。这些数据证明了多巴胺基因变异在阿片类药物依赖风险中的重要性,并突出了一个值得进一步研究的功能性多态性。