Variation in CYP2A6 Activity and Personalized Medicine.
Variation in CYP2A6 Activity and Personalized Medicine.
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DOI：
10.3390/jpm7040018
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发表时间：
2017-12-01
影响因子：
--
通讯作者：
Tyndale RF
中科院分区：
文献类型：
--
作者：
Tanner JA;Tyndale RF
细胞色素P450 2A 6（CYP 2A 6）酶代谢几种临床相关的底物，包括尼古丁-香烟烟雾中的主要精神活性成分。编码CYP 2A 6酶的基因具有高度多态性，导致CYP 2A 6酶活性以及尼古丁和其他CYP 2A 6底物（包括可替宁、替加氟、来曲唑、依法韦仑、丙戊酸、毛果芸香碱、青蒿素、青蒿琥酯、SM-12502、咖啡因和酪醇）的代谢速率存在广泛的个体间差异。CYP 2A 6的表达和活性也受到非遗传因素的影响，包括药理学、内源性和膳食物质的诱导或抑制，以及年龄相关变化，或与其他肝酶、辅酶和辅因子的相互作用。由于CYP 2A 6活性的变化与吸烟行为、戒烟、烟草相关肺癌风险以及代谢改变和导致的几种治疗的临床反应相关，因此CYP 2A 6表达和酶活性是重要的临床考虑因素。本文将讨论CYP 2A 6酶活性变异的来源，重点是CYP 2A 6遗传变异对CYP 2A 6底物代谢的影响。
The cytochrome P450 2A6 (CYP2A6) enzyme metabolizes several clinically relevant substrates, including nicotine—the primary psychoactive component in cigarette smoke. The gene that encodes the CYP2A6 enzyme is highly polymorphic, resulting in extensive interindividual variation in CYP2A6 enzyme activity and the rate of metabolism of nicotine and other CYP2A6 substrates including cotinine, tegafur, letrozole, efavirenz, valproic acid, pilocarpine, artemisinin, artesunate, SM-12502, caffeine, and tyrosol. CYP2A6 expression and activity are also impacted by non-genetic factors, including induction or inhibition by pharmacological, endogenous, and dietary substances, as well as age-related changes, or interactions with other hepatic enzymes, co-enzymes, and co-factors. As variation in CYP2A6 activity is associated with smoking behavior, smoking cessation, tobacco-related lung cancer risk, and with altered metabolism and resulting clinical responses for several therapeutics, CYP2A6 expression and enzyme activity is an important clinical consideration. This review will discuss sources of variation in CYP2A6 enzyme activity, with a focus on the impact of CYP2A6 genetic variation on metabolism of the CYP2A6 substrates.
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DOI：
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发表时间：
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期刊：
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影响因子：
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发表时间：
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影响因子：
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