CYP2C9 gene polymorphisms influence on antihypertensive effectiveness and hypouricemic effect of losartan among patients with arterial hypertension: an observational study.

Q2 Pharmacology, Toxicology and Pharmaceutics

Drug metabolism and personalized therapy Pub Date : 2023-06-01 DOI:10.1515/dmpt-2022-0115

Irina I Sinitsina, Alexey V Boyarko, Ilyas I Temirbulatov, Dmitry A Sychev, Kristina A Akmalova, Zhannet A Sozaeva, Elena A Grishina, Karin B Mirzaev, Anastasiia V Asoskova, Vladimir P Fisenko

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引用次数: 3

Abstract

Objectives: CYP2C9 gene polymorphic variants can decrease the effects of losartan, reducing active metabolite (E-3174) formation. Study aims to determine the influence of *2 (+430C>T; rs799853) and *3 (+1075A>C; rs1057910) CYP2C9 gene polymorphic variants on the hypotensive and uricosuric effect of losartan on patients with arterial hypertension.

Methods: Eighty one patients with stage 1-2 arterial hypertension newly diagnosed with ABMP were enrolled in the study. Physicians started losartan treatment and then we measured urine concentration of E-3174/losartan to estimate CYP2C9 activity. After 3-month losartan treatment we compared effectiveness of the therapy with ABPM and plasma uric acid level between carriers of CYP2C9 *1/*1 and CYP2C9 gene polymorphic variants (*2 and *3).

Results: Carriage of CYP2C9*2 and CYP2C9*3 alleles reduced the hypotensive effect of losartan (p<0.001, OR=8.13 (95% CI, 2.75-23.97)). Analysis of the ABPM data revealed that blood pressure was significantly higher in patients with polymorphic genotypes. There was no significant difference in uric acid level in plasma and losartan and its metabolite concentration in urine between genotypes.

Conclusions: Carriage of low function polymorphic variants of the CYP2C9 gene (*2 and *3) reduced the hypotensive effect of losartan according to ABPM and don't affect uric acid level in plasma and E-3174/losartan in urine.

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CYP2C9基因多态性对动脉性高血压患者氯沙坦降压效果和降糖效果的影响:一项观察性研究

目的:CYP2C9基因多态性变异可降低氯沙坦的作用，减少活性代谢物(E-3174)的形成。研究旨在确定*2 (+430C>T)的影响;rs799853)和*3 (+1075A>C;rs1057910) CYP2C9基因多态性变异对氯沙坦对高血压患者降压降尿作用的影响。方法:81例新诊断为ABMP的1-2期高血压患者入组研究。医生开始氯沙坦治疗，然后我们测量尿E-3174/氯沙坦浓度来估计CYP2C9活性。氯沙坦治疗3个月后，比较CYP2C9 *1/*1和CYP2C9基因多态性变异携带者(*2和*3)的ABPM和血浆尿酸水平。结果:携带CYP2C9*2和CYP2C9*3等位基因可降低氯沙坦的降压作用(p结论:携带CYP2C9基因*2和*3低功能多态性变异可根据ABPM降低氯沙坦的降压作用，但不影响血浆尿酸水平和尿E-3174/氯沙坦。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Drug metabolism and personalized therapy Pharmacology, Toxicology and Pharmaceutics-Pharmacology, Toxicology and Pharmaceutics (all)

CiteScore

2.30

自引率

0.00%

发文量

期刊介绍： Drug Metabolism and Personalized Therapy (DMPT) is a peer-reviewed journal, and is abstracted/indexed in relevant major Abstracting Services. It provides up-to-date research articles, reviews and opinion papers in the wide field of drug metabolism research, covering established, new and potential drugs, environmentally toxic chemicals, the mechanisms by which drugs may interact with each other and with biological systems, and the pharmacological and toxicological consequences of these interactions and drug metabolism and excretion. Topics: drug metabolizing enzymes, pharmacogenetics and pharmacogenomics, biochemical pharmacology, molecular pathology, clinical pharmacology, pharmacokinetics and drug-drug interactions, immunopharmacology, neuropsychopharmacology.