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小白蛋白基因启动子区DNA甲基化增加与甲基苯丙胺依赖有关。

Increased DNA methylation in the parvalbumin gene promoter is associated with methamphetamine dependence.

作者信息

Veerasakul Siriluk, Watiktinkorn Paritat, Thanoi Samur, Dalton Caroline F, Fachim Helene A, Nudmamud-Thanoi Sutisa, Reynolds Gavin P

机构信息

Department of Anatomy, Faculty of Medical Science, Naresuan University, Phitsanulok, 65000, Thailand.

Centre of Excellence in Medical Biotechnology, Faculty of Medical Science, Naresuan University, Phitsanulok, 65000, Thailand.

出版信息

Pharmacogenomics. 2017 Sep;18(14):1317-1322. doi: 10.2217/pgs-2016-0188. Epub 2017 Aug 24.

Abstract

AIM

The parvalbumin (PV)-containing subgroup of GABAergic neurons is particularly affected in schizophrenia and animal models of psychosis, including after methamphetamine (METH) administration. We investigated whether METH dependence and METH-induced psychosis may involve an effect on DNA methylation of the PVALB promoter.

MATERIALS & METHODS: The methylation of a PVALB promoter sequence was determined in 100 METH-dependent and 102 control subjects using pyrosequencing.

RESULTS

A significant increase in PVALB methylation was observed in METH dependence and METH-induced psychosis. No significant effect on long interspersed nucleotide element-1 methylation, a measure of global DNA methylation, was observed.

CONCLUSION

These results demonstrate a specific association between elevated PVALB methylation and METH-induced psychosis. This finding may contribute to the GABAergic deficits associated with METH dependence.

摘要

目的

含小白蛋白(PV)的γ-氨基丁酸能神经元亚群在精神分裂症和精神病动物模型中受到特别影响,包括在给予甲基苯丙胺(冰毒)之后。我们研究了冰毒依赖和冰毒诱发的精神病是否可能涉及对小白蛋白(PVALB)启动子DNA甲基化的影响。

材料与方法

使用焦磷酸测序法在100名冰毒依赖者和102名对照受试者中测定PVALB启动子序列的甲基化情况。

结果

在冰毒依赖和冰毒诱发的精神病中观察到PVALB甲基化显著增加。未观察到对长散在核元件-1甲基化(一种整体DNA甲基化的指标)有显著影响。

结论

这些结果表明PVALB甲基化升高与冰毒诱发的精神病之间存在特定关联。这一发现可能有助于解释与冰毒依赖相关的γ-氨基丁酸能缺陷。

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