Raunio Hannu, Rahnasto-Rilla Minna
Faculty of Health Sciences, School of Pharmacy, University of Eastern Finland, Kuopio, Finland.
Drug Metabol Drug Interact. 2012 May 5;27(2):73-88. doi: 10.1515/dmdi-2012-0001.
The human CYP2A gene subfamily consists of three members, CYP2A6, CYP2A7, and CYP2A13. The CYP2A6 gene is highly polymorphic with approximately 40 annotated allelic variants. Individuals homozygous for some of these alleles have a total lack of CYP2A6 activity. The CYP2A6 protein is most abundant in liver and is expressed, although at much lower levels, in some other tissues, especially nasal mucosa. CYP2A6 differs from other human liver CYP forms in that it participates in the metabolism of very few currently used drugs. The two most relevant substrates for CYP2A6 are coumarin and nicotine. Coumarin is the marker substance for determining CYP2A6 activity both in vitro and in vivo. Approximately 80% of a nicotine dose is eliminated by CYP2A6, and there is a clear link between CYP2A6 genotypes, smoking behavior, and lung cancer risk.
人类CYP2A基因亚家族由三个成员组成，即CYP2A6、CYP2A7和CYP2A13。CYP2A6基因具有高度多态性，大约有40个注释的等位基因变体。其中一些等位基因的纯合个体完全缺乏CYP2A6活性。CYP2A6蛋白在肝脏中含量最高，在其他一些组织中也有表达，尽管表达水平低得多，尤其是鼻黏膜。CYP2A6与其他人类肝脏CYP形式的不同之处在于它参与代谢的当前使用药物极少。CYP2A6的两个最相关底物是香豆素和尼古丁。香豆素是体外和体内测定CYP2A6活性的标志物。大约80%的尼古丁剂量由CYP2A6消除，并且CYP2A6基因型、吸烟行为和肺癌风险之间存在明确的联系。
