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首页> 外文期刊>Journal of Personalized Medicine >The Making of a CYP3A Biomarker Panel for Guiding Drug Therapy
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The Making of a CYP3A Biomarker Panel for Guiding Drug Therapy

机译：指导药物治疗的CYP3A生物标志物面板的制作

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CYP3A ranks among the most abundant cytochrome P450 enzymes in the liver, playing a dominant role in metabolic elimination of clinically used drugs. A main member in CYP3A family, CYP3A4 expression and activity vary considerably among individuals, attributable to genetic and non-genetic factors, affecting drug dosage and efficacy. However, the extent of genetic influence has remained unclear. This review assesses current knowledge on the genetic factors influencing CYP3A4 activity. Coding region CYP3A4 polymorphisms are rare and account for only a small portion of inter-person variability in CYP3A metabolism. Except for the promoter allele CYP3A4*1B with ambiguous effect on expression, common CYP3A4 regulatory polymorphisms were thought to be lacking. Recent studies have identified a relatively common regulatory polymorphism, designated CYP3A4*22 with robust effects on hepatic CYP3A4 expression. Combining CYP3A4*22 with CYP3A5 alleles *1, *3 and *7 has promise as a biomarker predicting overall CYP3A activity. Also contributing to variable expression, the role of polymorphisms in transcription factors and microRNAs is discussed.
机译：CYP3A是肝脏中最丰富的细胞色素P450酶之一，在临床使用药物的代谢消除中起主要作用。 CYP3A4是CYP3A家族的主要成员，在个体间CYP3A4的表达和活性差异很大，这归因于遗传和非遗传因素，影响药物的剂量和疗效。但是，遗传影响的程度仍不清楚。该评价评估了关于影响CYP3A4活性的遗传因素的最新知识。编码区CYP3A4多态性很少见，仅占CYP3A代谢中人际变异性的一小部分。除了启动子等位基因CYP3A4 * 1B对表达的影响不明确外，人们认为缺乏常见的CYP3A4调控多态性。最近的研究已经确定了一种相对常见的调节多态性，称为CYP3A4 * 22，对肝脏CYP3A4的表达具有强烈的影响。将CYP3A4 * 22与CYP3A5等位基因* 1，* 3和* 7结合起来有望作为预测整体CYP3A活性的生物标记。同样有助于变量表达，讨论了多态性在转录因子和microRNA中的作用。

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