Losartan monotherapy reduced systolic blood pressure significantly more in hypertensive patients with ABCB1 C3435T CT/TT genotypes (11.8%) compared to those with the CC genotype (6.7%).
Does the C3435T genetic polymorphism of the ABCB1 gene predict the antihypertensive efficacy of losartan monotherapy in patients with newly diagnosed arterial hypertension?
Carriers of the T allele (CT/TT genotypes) for the C3435T polymorphism of the ABCB1 gene demonstrate a significantly greater systolic blood pressure reduction from losartan monotherapy compared to CC homozygotes.
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.
Shelekhova et al. (2026) studied this question. Losartan monotherapy reduced systolic blood pressure significantly more in hypertensive patients with ABCB1 C3435T CT/TT genotypes (11.8%) compared to those with the CC genotype (6.7%).