The CYP2C9 genotype predicts the blood pressure response to irbesartan:: results from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation vs Atenolol (SILVHIA) trial
The CYP2C9 genotype predicts the blood pressure response to irbesartan:: results from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation vs Atenolol (SILVHIA) trial
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DOI：
10.1097/00004872-200210000-00030
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发表时间：
2002-10-01
影响因子：
4.9
通讯作者：
Melhus, H
中科院分区：
文献类型：
--
作者：
Hallberg, P;Karlsson, J;Melhus, H
细胞色素P450 CYP2C9酶（CYP2C9）代谢许多临床上重要的药物，如苯妥英、华法林和血管紧张素II型1 （AT）受体拮抗剂、氯沙坦和厄贝沙坦。CYP2C9基因的单核苷酸多态性导致CYP2C9*1（野生型）、CYP2C9*2和CYP2C9*3三个重要变体的表达，后两个变体的催化活性较野生型降低。已知CYP2C9基因型决定了华法林和苯妥英的敏感性和剂量要求，也决定了氯沙坦的代谢率。然而，它对AT(1)受体拮抗剂厄贝沙坦治疗的临床反应的影响尚未被研究。目的探讨CYP2C9基因型对厄贝沙坦降压疗效的影响。设计与方法将102例原发性高血压合并左心室肥厚患者随机分为厄贝沙坦组（n = 49）和β(1)-肾上腺素受体阻滞剂阿替洛尔组（n = 53）。在治疗前后12周测量血压，采用固相微序列法进行CYP2C9基因分型。结果厄贝沙坦患者的舒张压（DBP）反应与CYP2C9基因型不同，基因型为CYP2C9*1/CYP2C9*1的患者（n = 33）降低7.5%，基因型为CYP2C9*1/CYP2C9*2的患者（n = 12）降低14.4% （P = 0.036）。收缩压也有类似的趋势。相比之下，CYP2C9基因型与阿替洛尔（一种不通过CYP2C9代谢的药物）的血压反应之间没有关系。结论CYP2C9基因型似乎可以预测原发性高血压患者舒张压对厄贝沙坦的反应，而不是对阿替洛尔的反应。[J]中国生物医学工程学报，20(3):391 - 391。
Background The cytochrome P450 CYP2C9 enzyme (CYP2C9) metabolizes many clinically important drugs, for example, phenytoin, warfarin and the angiotensin II type 1 (AT,) receptor antagonists, losartan and irbesartan. Single nucleotide polymorphisms in the CYP2C9 gene result in the expression of three important variants, CYP2C9*1 (wild-type), CYP2C9*2 and CYP2C9*3, the last two exhibiting reduced catalytic activity compared with the wild-type. The CYP2C9 genotype is known to determine sensitivity to and dose requirements for both warfarin and phenytoin, and also the rate of metabolism of losartan. However, its influence on clinical response to treatment with the AT(1) receptor antagonist, irbesartan, has not been investigated.Objective To determine whether the CYP2C9 genotype influences the blood pressure-decreasing response to antihypertensive treatment with irbesartan.Design and methods One hundred and two patients with essential hypertension and left ventricular hypertrophy were allocated randomly to groups to receive double-blind treatment with either irbesartan (n = 49) or the beta(1)-adrenergic receptor blocker, atenolol (n = 53). Blood pressure was measured before and after 12 weeks of treatment CYP2C9 genotyping was performed using solid-phase minisequencing.Results The diastolic blood pressure (DBP) response differed in relation to the CYP2C9 genotype in patients given irbesartan: the reduction in patients with genotype CYP2C9*1/CYP2C9*1 (n = 33) was 7.5% and that with CYP2C9*1/CYP2C9*2 (n = 12) was 14.4% (P = 0.036). A similar trend was seen for systolic blood pressure. In contrast no relation was seen between the CYP2C9 genotype and blood pressure response to atenolol, a drug not metabolized via CYP2C9.Conclusions The CYP2C9 genotype seems to predict the DBP response to irbesartan, but not to atenolol, in patients with essential hypertension. J Hypertens 20:2089-2093 (C) 2002 Lippincott Williams Wilkins.