- 期刊
CYP2C19基因多型性在臨床藥物基因體篩檢的重要性
The Importance of Detection of CYP2C19 Genetic Polymorphism in Clinical Pharmacogenetics
摘要
Cytochrome P450是肝臟內用來代謝藥物的一群酵素。CYP2C19屬其中一類，專門代謝clopidogrel、proton pump inhibitors等藥物。其中clopidogrel是一種抑制血小板凝集功能的藥物，常用在心肌梗塞、心室顫動等心血管疾病的患者，或接受冠狀動脈支架置入手術後常服用的藥物。CYP2C19的基因多型性（Single nucleotide polymorphism, SNP）會影響酵素本身的活性，改變血液中藥物的濃度與代謝速率，影響藥物的臨床效用。目前已知CYP2C19基因有25種多型性變異，其中CYP2C19*2與CYP2C19*3基因型對clopidogrel的代謝率較差，擁有此基因型者為poor metabolizer（PM），在用藥後效果多不如預期，易引起血栓。而CYP2C19*17基因型對clopidogrel的代謝率會增加，為ultra rapid metabolizer（UM），增加血流不止的危險性。亞洲的中國人與台灣人比白種人有較高比例出現CYP2C19*2（台灣人：32%；白種人：15%）與CYP2C19*3（台灣人：5.5%；白種人：0%）。因此，在東方國家，檢測CYP2C19基因型對臨床clopidogrel的用藥是非常重要的參考。
並列摘要
Cytochrome P450 is a family of enzymes involved in drug metabolism in liver. One of the enzymes, CYP2C19, is involved in the metabolism of several drugs including proton pump inhibitor and clopidogrel. Clopidogrel is an antiplatelet agent which prevents platelet aggregation and is used for treatment of cardiovascular disease. Previous studies have shown that single nucleotide polymorphisms (SNPs) of CYP2C19 determine the enzyme activity and influence the metabolic rate of its substrates. There are 25 known polymorphic variants of the CYP2C19 gene. Among them, the genotypes CYP2C19*2 and CYP2C19*3 are correlated to complete loss of enzymatic activity to clopidogrel. People with genotypes CYP2C19*2 or CYP2C19*3 are poor metabolizer (PM) and easily develop ischemic events after treatment. In contrast, People with the genotype CYP2C19*17 are ultra-rapid metabolizer which have increased CYP2C19 activity and higher bleeding risk after clopidogrel treatment. Hence, identification of CYP2C19 genotypes provides useful information for therapeutic decision.The prevalence of different CYP2C19 alleles varies by ethnicity. The frequencies of alleles CYP2C19*2 and CYP2C19*3 (PM) in Caucasians are 15% and 0%, respectively; 36.6% and 7.5% in Chinese Han; and 32% and 5.5% in Taiwan. It reveals that Asians have a relatively high frequency of CYP2C19 PMs than Westerns. Therefore, it is very important to set up an appropriate CYP2C19 SNP test in our country.