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
{"title":"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","authors":"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","doi":"10.1515/dmpt-2022-0115","DOIUrl":null,"url":null,"abstract":"<p><strong>Objectives: </strong><i>CYP2C9</i> gene polymorphic variants can decrease the effects of losartan, reducing active metabolite (E-3174) formation. Study aims to determine the influence of <i>*2</i> (+430C>T; rs799853) and *3 (+1075A>C; rs1057910) <i>CYP2C9</i> gene polymorphic variants on the hypotensive and uricosuric effect of losartan on patients with arterial hypertension.</p><p><strong>Methods: </strong>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 <i>CYP2C9 *1/*1</i> and <i>CYP2C9</i> gene polymorphic variants (<i>*2</i> and <i>*3</i>).</p><p><strong>Results: </strong>Carriage of <i>CYP2C9*2</i> and <i>CYP2C9*3</i> 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.</p><p><strong>Conclusions: </strong>Carriage of low function polymorphic variants of the <i>CYP2C9</i> gene (<i>*2</i> and <i>*3</i>) reduced the hypotensive effect of losartan according to ABPM and don't affect uric acid level in plasma and E-3174/losartan in urine.</p>","PeriodicalId":11332,"journal":{"name":"Drug metabolism and personalized therapy","volume":"38 2","pages":"163-168"},"PeriodicalIF":0.0000,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"3","resultStr":"{\"title\":\"<i>CYP2C9</i> gene polymorphisms influence on antihypertensive effectiveness and hypouricemic effect of losartan among patients with arterial hypertension: an observational study.\",\"authors\":\"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\",\"doi\":\"10.1515/dmpt-2022-0115\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objectives: </strong><i>CYP2C9</i> gene polymorphic variants can decrease the effects of losartan, reducing active metabolite (E-3174) formation. Study aims to determine the influence of <i>*2</i> (+430C>T; rs799853) and *3 (+1075A>C; rs1057910) <i>CYP2C9</i> gene polymorphic variants on the hypotensive and uricosuric effect of losartan on patients with arterial hypertension.</p><p><strong>Methods: </strong>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 <i>CYP2C9 *1/*1</i> and <i>CYP2C9</i> gene polymorphic variants (<i>*2</i> and <i>*3</i>).</p><p><strong>Results: </strong>Carriage of <i>CYP2C9*2</i> and <i>CYP2C9*3</i> 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.</p><p><strong>Conclusions: </strong>Carriage of low function polymorphic variants of the <i>CYP2C9</i> gene (<i>*2</i> and <i>*3</i>) reduced the hypotensive effect of losartan according to ABPM and don't affect uric acid level in plasma and E-3174/losartan in urine.</p>\",\"PeriodicalId\":11332,\"journal\":{\"name\":\"Drug metabolism and personalized therapy\",\"volume\":\"38 2\",\"pages\":\"163-168\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2023-06-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"3\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Drug metabolism and personalized therapy\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1515/dmpt-2022-0115\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"Pharmacology, Toxicology and Pharmaceutics\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Drug metabolism and personalized therapy","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1515/dmpt-2022-0115","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"Pharmacology, Toxicology and Pharmaceutics","Score":null,"Total":0}
CYP2C9 gene polymorphisms influence on antihypertensive effectiveness and hypouricemic effect of losartan among patients with arterial hypertension: an observational study.
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.
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.
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