Key result
ABCB1 3435T carriage linked to ~5-point greater 6-week SBP reduction with losartan vs. CC homozygotes.
Why the study?
ABCB1 polymorphisms C3435T and C1236T may affect P-glycoprotein activity and modulate losartan efficacy, but their correlation with blood pressure response in newly diagnosed arterial hypertension was unknown.
Does the ABCB1 (MDR1) C3435T or C1236T genetic polymorphism predict the blood pressure reduction efficacy of 6-week losartan 100 mg/day monotherapy in patients with newly diagnosed stage I-II arterial hypertension?
Cohort (n=34)
No
Does the ABCB1 (MDR1) C3435T or C1236T genetic polymorphism predict the blood pressure reduction efficacy of 6-week losartan 100 mg/day monotherapy in patients with newly diagnosed stage I-II arterial hypertension?
Carriers of the ABCB1 (MDR1) C3435T T allele (CT/TT genotypes) experienced a significantly greater systolic blood pressure reduction with 6-week losartan monotherapy than CC homozygotes, suggesting a potential role for pharmacogenetic testing in personalizing antihypertensive therapy.
ABCB1 C3435T may influence losartan SBP response; this observational association is hypothesis-generating and requires prospective validation.
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.
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Shelekhova et al. (2026) conducted a cohort in Newly diagnosed essential arterial hypertension stage I-II (n=34). ABCB1 (MDR1) C3435T CT/TT genotype on losartan 100 mg/day monotherapy vs. ABCB1 (MDR1) C3435T CC homozygous (wild-type) genotype on losartan 100 mg/day monotherapy was evaluated on Percentage reduction in systolic blood pressure (SBP) from baseline at 6 weeks (p=0.03). ABCB1 C3435T CT/TT genotype carriers treated with losartan 100 mg/day had a greater 6-week SBP reduction than CC homozygotes (11.8% vs 6.7%, p=0.03).
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