Antihypertensive efficacy and safety of amlodipine in patients with different genotypes for C3435T of the ABCB1 geneDownload in PDF
To study the antihypertensive efficacy and safety profile of amlodipine in patients with arterial hypertension and different genotypes for C3435T of the ABCB1 gene.
Material and methods
We enrolled 100 hypertensive patients (45 males and 55 females, average age of 48.8±8.3 years) into an open-label, prospective clinical study. All of them were treated with amlodipine at the starting dose of 5 mg daily for 12 weeks. We used PCR-RFLP (polymerase chain reaction and restriction fragment length polymorphism) to study genotypes for C3435T of the ABCB1 gene.
СС, CT and TT genotypes of ABCB1 were detected in 17, 53, and 30 patients, respectively. TT genotype was associated with a higher antyhypertensive efficacy of amlodipine compared with CC genotype (target blood pressure was achieved in 43.3% and 11.8% patients, respectively). At 2 weeks, amlodipine dose was doubled in 6 (11.3%) patients with CT genotype and 9 (52.9%) patients with CC genotype, while starting dose of amlodipine was effective in all patients with TT genotype. At 12 weeks, office systolic blood pressure in patients with СС, СТ, and ТТ genotypes decreased by 7.36, 8.40, and 9.07%, respectively. Average reduction of diastolic blood pressure in the same groups of patients was 4.12%, 4.98%, and 5.46%, respectively. Adverse reactions occured in 35.3% ot patients with CC genotype, 11.3% of patients with CT genotype, and 6.7% of patients with TT genotype. ANOVA analysis showed statistically significant differences between patients with CC and TT genotypes in the systolic blood pressure reduction (р=0.02), the blood pressure control (р=0.02), the need in doubling of amlodipine dose (р=0.04), and the occurence of adverse reactions (р=0.05).
In patients with arterial hypertension, TT genotype for C3435T of the ABCB1 gene was associated with a higher antihypertensive efficacy and a better safety profile of amlodipine, compared with CC genotype.
Pharmacogenetics, ABCB1 gene, polymorphic marker C3435T, gene polymorphism, hypertension, amlodipine, efficacy, tolerability.