Investigation of MDR1 Gene Polymorphism and Losartan Plasma
Concentration in Patients Undergoing Hypertensive Episodes While under
Losartan Treatment
Abstract
Aim: 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. Method: 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 PCR analysis was carried out
in order to determine the frequencies of the G2677T/A, C3435T and C1236T
genotypes. Plasma losartan and EXP3174 levels of the patients were
calculated using tandem mass spectrometry Findings: 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). Besides, no significant difference
was evident between G2677T/A, C3435T and C1236T genotypes with respect
to plasma losartan/EXP3174 concentration (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. Keywords: Losartan, MDR1, Genetic polymorphism, EXP3174,
Hypertension