The influence of ABCB1 (rs4148738) and CYP3A4*22 (rs35599367) gene polymorphisms on therapy with slow calcium channel blocker amlodipine in patients with essential arterial hypertension

Introduction. The efficacy of pharmacological treatment of arterial hypertension depends of many factors. Some of them are polymorphisms of ABCB1 and CYP3A genes which take part in drug metabolism. The aim of present study was to determine the influence of ABCB1 (rs4148738) and CYP3A4*22 (rs35599367) polymorphisms on the efficacy and safety of antihypertensive therapy with amlodipine. Methods. The study included 100 patients diagnosed with essential arterial hypertension (I-II stages) who received amlodipine, 53 of them are men and 47 are women (mean age 60.15 ± 10.31 years). Genotyping of ABCB1 (rs4148738) and CYP3A4*22 (rs35599367) polymorphisms was performed by reaL-time polymerase chain reaction. To evaluate the efficacy of antihypertensive therapy an office bLood pressure measurement was used before and after 12-week treatment with amlodipine. The safety of treatment was estimated by physical examination. Results. During the research of ABCB1 (rs4148738) polymorphism 19 patients with the CC genotype, 49 patients with the CT genotype and 32 with the TT genotype were identified. The distribution obeys the Hardy-Weinberg Law (х² = 0.001; p = 0.97) which indicates that the sample is representative. Comparison of the three groups of patients by ABCB1 polymorphism revealed significant differences in the frequency of adverse drug reactions caused by amlodipine treatment (Pearson’s chi-squared test, p = 0.02). The greatest number of them was observed in patients with the TT genotype, the minimal - in patients with the CC genotype. There were no statistically significant differences in the change of systolic (SBP) and diastolic (DBP) blood pressure between the three groups (Kruskal-Wallis test, p = 0.41 and p = 0.08 respectively). However when comparing patient groups carriers of at least one T-allele and non-carriers of this allele (CT + TT and CC) greater DBP reducing was found in patients with CC genotype (Mann-Whitney U test, p = 0.025). For the CYP3A4*22 (rs35599367) polymorphism the distribution was: 98 patients with CC genotype and 2 heterozygotes CT. Due to low genotype frequency of CT genotype it was impossible to estimate the role of this polymorphism in treatment with amlodipine. Conclusions. Based on the results obtained it can be concluded that lower efficacy of amlodipine in reducing DBP was performed in patients who are carriers of at least one T-allele. The genotype TT is most associated with the emergence of adverse effects while in patients with the CC genotype their frequency is minimal and for the CT genotype it is at an intermediate level.

фармакогенетика, полиморфизм, метаболизм лекарств, артериальная гипертензия, амлодипин, pharmacogenetics, polymorphism, drug metabolism, arterial hypertension, amlodipine

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