The C3435T genetic polymorphism of the ABCB1 (MDR1) gene as a predictor of antihypertensive efficacy of losartan monotherapy in newly diagnosed arterial hypertension

Авторы

DOI:

https://doi.org/10.18413/rrpharmacology.12.1057

Аннотация

Introduction: Losartan, a selective angiotensin II receptor type 1 antagonist, is transported across cell membrane mediated by P-glycoprotein, the product of the ABCB1 (also known as MDR1) gene. The level of expression of this transporter protein is characterized by significant individual variability, caused by genetic factors. Well-known polymorphisms C3435T and C1236T in the ABCB1 gene potentially could affect a functional activity of the P-glycoprotein, thus modulating the pharmacokinetic parameters and clinical efficacy of the substrates of this transporter, including losartan. Therefore, the aim of this research is to indicate the correlation between common SNPs C3435T and C1236T of the MDR1 gene and the efficacy of 6-week losartan monotherapy course in patients with a newly diagnosed arterial hypertension (AH).

Materials and Methods: The study included 34 patients (70.6% women, mean age 48.3 ± 7.4 years). All participants were given losartan 100 mg/day for 6 weeks. Genotyping for C3435T and C1236T polymorphisms was made by using allele-specific PCR with electrophoretic detection. The efficacy of the therapy was evaluated by the reduction of systolic (SBP) and diastolic (DBP) blood pressure from the reference level.

Results: Patients with CT or TT genotypes for the C3435T polymorphism showed a statistically meaningful, greater reduction in SBP (11.8% ± 9.7) compared to homozygous CC genotype (”wild” type; 6.7% ± 9.6; p=0.03). No significant differences were found in SBP reduction for the C1236T polymorphism (p=0.07). Changes in DBP did not correlate with either of the studied polymorphisms.

Conclusions: The C3435T genetic polymorphism of the MDR1 gene is a potential predictor of the efficacy of losartan antihypertensive therapy. The carriers of the T allele (CT/TT genotypes) demonstrate more expressed hypotensive response, which may be caused by modulation of tissue distribution of the drug or its interaction with endogenous systems (ouabain) regulating blood pressure. The obtained data highlights the importance of a pharmacogenetic approach for personalizing AH treatment.

Графическая аннотация

Ключевые слова:

P-glycoprotein, ABCB1, MDR1, genetic polymorphism, arterial hypertension, losartan, personalized medicine

Библиографические ссылки

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Вклад авторов

Татьяна В. Шелехова, Saratov State Medical University named after V.I. Razumovsky

Doctor Habil. of Medical Sciences, Professor, Head of the Department of Occupational Pathology, Hematology and Clinical Pharmacology, Saratov State Medical University named after V.I. Razumovsky of the Ministry of Health of Russia, Saratov, Russia; e-mail: tshelexova@mail.ru; ORCID ID: https://orcid.org/0000-0002-4737-7695. Study concept and design; manuscript writing and editing.

Артем В. Рута, Saratov State Medical University named after V.I. Razumovsky

Candidate of Medical Sciences, Associate Professor of the Department of Occupational Pathology, Hematology and Clinical Pharmacology, Saratov State Medical University named after V.I. Razumovsky of the Ministry of Health of Russia, Saratov, Russia; e-mail: artem_ruta@mail.ru; ORCID ID: https://orcid.org/0000-0001-6500-7877. Study concept and design, data collection, data analysis and processing of material; writing the text, refining and approving of the final version of the manuscript.

Елена В. Лучинина, Saratov State Medical University named after V.I. Razumovsky

Candidate of Medical Sciences, Associate Professor of the Department of Occupational Pathology, Hematology and Clinical Pharmacology, Saratov State Medical University named after V.I. Razumovsky of the Ministry of Health of Russia, Saratov, Russia; e-mail: eluchinina16@mail.ru; ORCID ID: https://orcid.org/0000-0002-3120-8491. Discussion of the results and concept of the study; writing the manuscript.

Роман А. Бонцевич, Mari State University

MD, PhD, physician, pulmonologist, clinical pharmacologist, Associate Professor of the Department of Internal Diseases No. 2 of Mari State University, Yoshkar-Ola, Russia; Associate Professor of the Department of Clinical Pharmacology and Pharmacotherapy of Kazan State Medical Academy – branch of the Russian Medical Academy of Continuous Professional Education, Kazan, Russia; e-mail: bontsevich@gmail.com; ORCID ID: https://orcid.org/0000-0002-9328-3905. Discussion of the results and concept of the study; refining and approving of the final version of the manuscript.

Марина Р. Зайцева, Saratov State Medical University named after V.I. Razumovsky

Candidate of Medical Sciences, Associate Professor of the Department of Occupational Pathology, Hematology and Clinical Pharmacology, Saratov State Medical University named after V.I. Razumovsky of the Ministry of Health of Russia, Saratov, Russia; e-mail: zayceva5505@mail.ru; ORCID ID: https://orcid.org/0000-0002-4875-5861. Discussion of the results and concept of the study; processing the material.

Александр Н. Леванов, State Medical University named after V.I. Razumovsky

Assistant of the Department of Occupational Pathology, Hematology and Clinical Pharmacology, Saratov State Medical University named after V.I. Razumovsky of the Ministry of Health of Russia, Saratov, Russia; e-mail: lewanowan@mail.ru; ORCID ID: https://orcid.org/0000-0003-4742-0881. Discussion of the results and concept of the study; editing the manuscript.

Полина А. Чередникова, Saratov State Medical University named after V.I. Razumovsky

Resident of the Department of Occupational Pathology, Hematology and Clinical Pharmacology, Saratov State Medical University named after V.I. Razumovsky of the Ministry of Health of Russia, Saratov, Russia; e-mail: cherednikovapolina@yandex.ru; ORCID ID: https://orcid.org/0009-0007-4009-2340. Discussion of the results and concept of the study; statistical data processing.

Евгений А. Лучинин, Saratov State Medical University named after V.I. Razumovsk

Assistant of the Department of Occupational Pathology, Hematology and Clinical Pharmacology, Saratov State Medical University named after V.I. Razumovsky of the Ministry of Health of Russia, Saratov, Russia; e-mail: gly10@gmail.com; ORCID ID: https://orcid.org/0000-0001-6304-4594. Discussion of the results and concept of the study; statistical data processing.

Загрузки

Опубликован

30.03.2026

Как цитировать

Shelekhova TV, Ruta AV, Luchinina EV, Bontsevich RA, Zaitсeva MR, Lewanow AN, Сherednikova PА, Luchinin EА (2026) The C3435T genetic polymorphism of the ABCB1 (MDR1) gene as a predictor of antihypertensive efficacy of losartan monotherapy in newly diagnosed arterial hypertension. Research Results in Pharmacology 12(1): 95–100. https://doi.org/10.18413/rrpharmacology.12.1057

Выпуск

Том 12 № 1 (2026)

Раздел

Короткое сообщение

Лицензия

Copyright (c) 2026 Shelekhova TV, Ruta АV, Luchinina ЕV, Bontsevich RA, Zaitсeva MR, Lewanov AN, Сherednikova PА, Luchinin EА

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