CYP2D6 in the brain: genotype effects on resting brain perfusion
CYP2D6 in the brain: genotype effects on resting brain perfusion
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DOI：
10.1038/mp.2010.42
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发表时间：
2011-03-01
影响因子：
11
通讯作者：
Viviani, R.
中科院分区：
文献类型：
--
作者：
Kirchheiner, J.;Seeringer, A.;Viviani, R.
细胞色素P450 2D 6（CYP 2D 6）是一种参与多种精神活性药物代谢的遗传多态性酶。除了在肝脏中表达外，CYP 2D 6还在大脑的几个区域中高度表达，如海马、丘脑、下丘脑和皮质，但其在大脑中的功能还不清楚。CYP 2D 6酶也可能由于其参与神经递质生物转化而具有生理作用。在这项研究中，CYP 2D 6基因分型进行了N = 188健康人，并与休息时的脑灌注水平，这可能反映了一个正在进行的生物过程，调节个体的反应性情绪刺激和检测信号引起的恐惧。相对于N = 42个匹配的快代谢者，N = 14个慢代谢者与丘脑中高15%的灌注水平相关（P = 0.03和0.003）。影响也存在于整个（N = 188）样品分为代谢组，或精细分级为7个CYP 2D 6活性水平。在右侧海马中观察到较弱的影响（P = 0.05）。一项扩展至全脑的探索性分析表明，CYP 2D 6参与了与警觉性或多巴胺能功能相关的区域。这些发现支持了CYP 2D 6在大脑中的功能作用的假设。Molecular Psychiatry（2011）16，333-341; doi：10.1038/mp.2010.42; 2010年4月6日在线发表
The cytochrome P450 2D6 (CYP2D6) is a genetically polymorphic enzyme involved in the metabolism of several psychoactive drugs. Beside its expression in the liver, CYP2D6 is highly expressed in several regions of the brain, such as the hippocampus, thalamus, hypothalamus and the cortex, but its function in the brain is not well understood. The CYP2D6 enzyme may also have a physiological role due to its involvement in neurotransmitter biotransformation. In this study, CYP2D6 genotyping was performed in N = 188 healthy individuals and compared with brain perfusion levels at rest, which may reflect an ongoing biological process regulating the reactivity of the individual to emotional stimuli and the detection of signals evoking fear. Relative to N = 42 matched extensive metabolizers, N = 14 poor metabolizers were associated with 15% higher perfusion levels in the thalamus (P = 0.03 and 0.003). Effects were also present in the whole (N = 188) sample divided into metabolizer groups, or finely graded into seven CYP2D6 activity levels. A weaker effect was observed in the right hippocampus (P = 0.05). An exploratory analysis, extended to the whole brain, suggested the involvement of CYP2D6 in regions associated with alertness or serotonergic function. These findings support the hypothesis of a functional role of CYP2D6 in the brain. Molecular Psychiatry (2011) 16, 333-341; doi:10.1038/mp.2010.42; published online 6 April 2010