The influence of CYP2C9 gene polymorphisms on the efficacy of losartan in patients with grade I-II arterial hypertension


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Abstract

Background. Angiotensin II receptor antagonists (ARAII, sartans) are one of the drugs of choice in the treatment of arterial hypertension (AH). The use of antihypertensive drugs is not equally effective for all patients. Losartan is metabolized to an active metabolite by cytochrome CYP2C9. The gene encoding this enzyme has several polymorphisms that affect its activity. Objective. Assesment of the effect of CYP2C9 gene polymorphisms on the hypotensive efficacy of therapy with losartan. Methods. The study included 81 patients. At the first stage, 24-hour blood pressure monitoring and genotyping for CYP2C9*2 and CYP2C9*3 allele variants were performed. Against the background of monotherapy with losartan, the activity of the CYP2C9 isoenzyme was assessed as the E-3174 losartan metabolite/ losartan concentration in the urine ratio. Depending on the results of CYP2C9 genotyping, the patients were divided into two comparison groups: the first group - carriers of the CYP2C9*1/*1 allele and the second ones - carriers of the CYP2C9*2, CYP2C9*3 alleles. At the second stage, 3 months after, various parameters of 24-hour blood pressure monitoring and the effectiveness of the therapy between the two groups were assessed. Results. An association of CYP2C9 polymorphic alleles with ineffectiveness of losartan therapy was revealed (OR=8.13, 95% CI 2.75-23.98). Comparative analysis of 24-hour blood pressure monitoring data showed that mean and maximum systolic and diastolic blood pressure at the end of the study was significantly higher in carriers of CYP2C9*2 and *3 allele variants. The deltas between the 24-hour blood pressure monitoring values before and after therapy were significantly higher in carriers of the CYP2C9*1/*1 variant. The results of a pharmacokinetic study did not reveal any effect of CYP2C9 gene polymorphisms on the concentration of losartan and its metabolite in urine. Conclusion. Carriage of allelic variants CYP2C9*2 and CYP2C9*3 is associated with a decrease in the hypotensive effect of losartan.

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About the authors

I. I Sinitsina

Russian Medical Academy of Continuous Professional Education

Moscow, Russia

A. V Boyarko

LMS Clinic

Moscow, Russia

Ilyas I Temirbulatov

Russian Medical Academy of Continuous Professional Education

Email: temirbulatov.ilyas@gmail.com
Resident at the Department of Clinical Pharmacology and Therapy Moscow, Russia

K. B Mirzaev

Russian Medical Academy of Continuous Professional Education

Moscow, Russia

E. A Grishina

Russian Medical Academy of Continuous Professional Education

Moscow, Russia

Zh. A Sozaeva

Russian Medical Academy of Continuous Professional Education

Moscow, Russia

K. A Akmalova

Russian Medical Academy of Continuous Professional Education

Moscow, Russia

G. N Shuev

Russian Medical Academy of Continuous Professional Education

Moscow, Russia

N. P Denisenko

Russian Medical Academy of Continuous Professional Education

Moscow, Russia

A. A Kachanova

Russian Medical Academy of Continuous Professional Education

Moscow, Russia

D. A Sychev

Russian Medical Academy of Continuous Professional Education

Moscow, Russia

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