CYP2C9 gene polymorphisms influence on antihypertensive effectiveness and hypouricemic effect of losartan among patients with arterial hypertension: an observational study.
| Autor: | Sinitsina II; Department of Clinical Pharmacology and Therapeutics, Russian Medical Academy of Continuous Professional Education, Moscow, Russian Federation., Boyarko AV; Department of Clinical Pharmacology and Therapeutics, Russian Medical Academy of Continuous Professional Education, Moscow, Russian Federation., Temirbulatov II; Department of Clinical Pharmacology and Therapeutics, Russian Medical Academy of Continuous Professional Education, Moscow, Russian Federation.; Laboratory of Human Population Genetics, Research Centre for Medical Genetics, Moscow, Russia., Sychev DA; Department of Clinical Pharmacology and Therapeutics, Russian Medical Academy of Continuous Professional Education, Moscow, Russian Federation., Akmalova KA; Department of Molecular Medicine, Russian Medical Academy of Continuous Professional Education, Moscow, Russian Federation., Sozaeva ZA; Department of Molecular Medicine, Russian Medical Academy of Continuous Professional Education, Moscow, Russian Federation., Grishina EA; Department of Molecular Medicine, Russian Medical Academy of Continuous Professional Education, Moscow, Russian Federation., Mirzaev KB; Laboratory of Human Population Genetics, Research Centre for Medical Genetics, Moscow, Russia.; Department of Molecular Medicine, Russian Medical Academy of Continuous Professional Education, Moscow, Russian Federation., Asoskova AV; Department of Dermatovenerology and Cosmetology, Russian Medical Academy of Continuous Professional Education, Moscow, Russian Federation., Fisenko VP; Department of Pharmacology, Institute of Clinical Medicine, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russian Federation. |
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| Jazyk: | angličtina |
| Zdroj: | Drug metabolism and personalized therapy [Drug Metab Pers Ther] 2022 Dec 29; Vol. 38 (2), pp. 163-168. Date of Electronic Publication: 2022 Dec 29 (Print Publication: 2023). |
| DOI: | 10.1515/dmpt-2022-0115 |
| Abstrakt: | 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. (© 2022 Walter de Gruyter GmbH, Berlin/Boston.) |
| Databáze: | MEDLINE |
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