药物基因组学对美托洛尔疗效剂量的影响-第三军医大学学报.doc

药物基因组学对美托洛尔疗效的影响* （中央民族大学，北京 100081）摘要: 目的 评述药物基因组学对美托洛尔疗效的影响。以国内外研究文献为基础根据美托洛尔治疗原发性高血压、心血管疾病作用机制及体内代谢机制从药物基因组学角度对影响美托洛尔疗效因素进行评述。 （1）β1肾上腺素受体基因1165C突变导致受体敏感性增加，是影响美托洛尔疗效的因素之一，145G突变对美托洛尔疗效的影响尚不明确（2）CYP2D6*10多态性可显著改变美托洛尔的药代动力学，但对其降压疗效无显著影响（3）β3亚基C825T多态性使美托洛尔治疗后叶尖收缩压及舒张压下降增强并与β1肾上腺素受体基因1165C突变联合对美托洛尔心血管效应影响；β受体阻滞药对α亚基基因T393C基因型显著降压作用，但对美托洛尔的具体影响尚不明确。 虽然多种基因多态性都对美托洛尔的疗效产生影响，但比较而言β1肾上腺受体和G蛋白基因是美托洛尔个体间疗效差异的决定因素。 关键词：美托洛尔；药物基因组学；心血管疾病 The Influence on Metoprolol Curative Effect of Pharmacogenomics* Li Shun-chun*，W Huai（Beijing 100081） : OBJECTIVE This paper is focused on the affectation on the efficacy of metoprolol of the β1 adrenaline receptor gene,CYP2D6 enzyme gene and G protein gene polymorphism. METHODS On the base of domestic and international research and the mechanism of treatment on hypertension,cardiovascular disease of Metoprolol, factors of Metoprolol curative effect are reviewed from drug genomics angle. RESULTS (1) ADRB1 G1165C affect curative effect of Metoprolol,the effect of mutation A145G on Metoprolol is not clear. (2) CYP2D6 * 10 polymorphism can significantly change the Metoprolol pharmacokinetic,but no significant influence of the antihypertensive effects was found. (3) GNB3 mutation C825T makes tip systolic blood pressure and diastolic pressure drops strengther after Metoprolol treatment to, and combination with ADRB1 mutations G1165C affect Metoprolol effect of cardiovascular;β receptor blockade medicine have significant antihypertensive effect on GNAS1 mutation T393C gene type,but influence on Metoprolol is not clear. CONCLUSION Although many of the genetic polymorphism affect Metoprolol curative effect,but in comparison,ADRB1 and G protein genetic polymorphism is the decisive factor which caused individual differences of Metoprolol. KEYWORDS: metoprolol; pharmacogenomics; cardiovascular disease 自20世纪50年代开始由原发性高血压及其他因素引发的心血管疾病已成为世界主要致死原因之一，严重威胁着人类的生命健康[1]。美托洛尔心脏选择性β1受体阻断剂[2]，作为经典的治疗高血压及心血管疾病药物广泛应用于临床治疗。然而大量资料表明，美托洛尔的疗效显示出明显的个体差异性，临床较易发生药物不良反