Investigation of MDR1 Gene Polymorphism and Losartan Plasma Concentration in Patients Undergoing Hypertensive Episodes While under Losartan Treatment

Abstract

Purpose: Losartan, a drug in the angiotensin receptor blocker (ARB) family, is the substrate of the Multi Drug Resistance-1 (MDR1) drug-efflux protein encoded by the ABCB1 gene. This study seeks to investigate the MDR1 gene polymorphism and losartan concentration in order to identify drug resistance in patients presenting to the emergency department (ED) with a hypertensive episode while having losartan treatment. Methods: The ethics approval of our study was granted by Gazi University Clinical Research Ethics Committee (dateof registration 23.10.2017, number: 496) and Ministry of Health Turkey Medicines and Medical Devices Agency (date of registration 14.02.2018, code number: 17-AKD-189). The patient cohort was comprised of 50 individuals presenting with a hypertensive episode while under losartan treatment. The control cohort included 50 patients whose blood pressure was regulated while receiving losartan treatment and who were admitted to the ED for reasons other than hypertensive episode. Allele-specific analysis was carried out PCR (Polymerase Chain Reaction) device. Plasma losartan and EXP3174 levels of the patients were measured using tandem mass spectrometry. Results: The frequencies of GG, GT, GA, TA and TT genotypes did not differ significantly between the cohorts in G2677T/A single nucleotide polymorphism (SNP) (p>0.05), whereas those of C3435T TT and C1236T CT genotypes yielded a significant difference between the patient and control cohorts (p<0.05). Conclusion: We provided clinical evidence that hypertensive episodes occurred more frequently in C3435T TT and less frequently in C1236T CT. However, no significant correlation was established between plasma losartan, EXP3174 concentration and G2677T/A, C3435T, and C1236T genotypes. American Clinical Trials Registration Number: NCT05349825