阿片类药物成瘾中的多巴胺基因变异：依赖患者、非依赖使用者与健康对照的比较
Dopamine gene variants in opioid addiction: comparison of dependent patients, nondependent users and healthy controls.
作者信息
Randesi Matthew, van den Brink Wim, Levran Orna, Yuferov Vadim, Blanken Peter, van Ree Jan M, Ott Jurg, Kreek Mary Jeanne
机构信息
Laboratory of the Biology of Addictive Diseases, The Rockefeller University, 1230 York Ave, New York, NY 10065, USA.
Central Committee on the Treatment of Heroin Addicts (CCBH), Universiteitsweg 100, 3584 CG Utrecht, The Netherlands.
出版信息
Pharmacogenomics. 2018 Jan;19(2):95-104. doi: 10.2217/pgs-2017-0134. Epub 2017 Dec 6.
Abstract
AIM
To determine whether specific dopaminergic system gene variants are associated with opioid dependence.
PATIENTS & METHODS: Subjects included 153 healthy controls, 163 opioid exposed, but not dependent and 281 opioid dependent. Genotypes of 90 variants in 13 genes were examined.
RESULTS
The most significant results were obtained for DA β-hydroxylase variants, rs2073837 and rs1611131, which were associated with protection from addiction (q = 0.0172, 0.0415, respectively) and the functional TH variant, rs2070762, was associated with more risk (q = 0.0387). The three variants also showed a combined effect that remained significant after correction for multiple testing (p = 0.0039).
CONCLUSION
These data offer support that dopaminergic gene variants have a role in opioid dependence and warrant further study.
摘要
目的
确定特定的多巴胺能系统基因变异是否与阿片类药物依赖有关。
患者与方法
受试者包括153名健康对照者、163名暴露于阿片类药物但未成瘾者以及281名阿片类药物成瘾者。检测了13个基因中90个变异的基因型。
结果
多巴胺β-羟化酶变异rs2073837和rs1611131的结果最为显著，它们与预防成瘾有关（分别为q = 0.0172、0.0415），而功能性酪氨酸羟化酶变异rs2070762与更高风险有关（q = 0.0387）。这三个变异还显示出一种联合效应，在多重检验校正后仍具有显著性（p = 0.0039）。
结论
这些数据支持多巴胺能基因变异在阿片类药物依赖中起作用，值得进一步研究。
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2
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Ann Hum Genet. 2015 May;79(3):188-98. doi: 10.1111/ahg.12104. Epub 2015 Feb 27.
3
Dopaminergic pathway polymorphisms and heroin addiction: further support for association of CSNK1E variants.多巴胺能通路基因多态性与海洛因成瘾：对CSNK1E变体关联的进一步支持。
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