An open, non-comparative, prospective clinical study was conducted to evaluate the antihypertensive efficacy and tolerability of amlodipine, a calcium antagonist, in patients with arterial hypertension (AH) I-II stages, depending on the genotype for the polymorphic marker C3435T of the ABCB1 gene. The study included 100 patients with AH I-II stages, aged from 45 to 58 years. The initial dose of amlodipine was 5 mg, duration of treatment was 12 weeks. General clinical examination methods, office measurement and daily blood pressure monitoring, tolerance evaluation, and genotyping using the ABCB1 polymorphic marker C3435T by the PCR-RFLP method (polymerase chain reaction and restriction fragment length polymorphism) were used. The statistical analysis of results was carried out using the Mann-Whitney U test for quantitative variables, Kruskal-Wallis one-way analysis of variance (ANOVA) for three independent groups of quantitative data. Excellent antihypertensive efficacy with the CC genotype was found in 11.8% patients, with CT - 33.9%, with TT - 43.3%; good - 35.3%, 32.1%, and 33.3% respectively, satisfactory - 52.9%, 34,0% and 23.4% respectively. Six patients with the CT genotype and nine patients with the CC genotype required the increase in the dose to 10 mg. The number of patients with Adverse drug reactions (ADR) were found in 35.3% of patients with the CC genotype, 6.7% with the TT genotype and 11.3% with the CT genotype. The Kruskal-Wallis test revealed significant differences between CC and TT genotypes in the degree of decrease in SBP (p=0.02), antihypertensive efficacy parameter (p=0.02), an increase in dose requirements (p = 0.04) and the incidence of ADR(p=0.05). In AH patients (I-II stage) with the TT genotype of the C3435T gene polymorphism one can expect higher rates of antihypertensive efficacy of amlodipine in combination with a good safety profile and the lowest ADR percentage, while patients with the CC genotype more likely to develop ADR and lower antihypertensive responsiveness.
Provedeno otkrytoe nesravnitel'noe prospektivnoe klinicheskoe issledovanie po otsenke antigipertenzivnoĭ éffektivnosti i perenosimosti antagonista kal'tsiia amlodipina u bol'nykh AG I-II stepeni v zavisimosti ot genotipa po polimorfnomu markeru S3435T gena ABCB1. V issledovanie vkliucheno 100 bol'nykh AG I-II stepeni v vozraste ot 45 do 58 let. Nachal'naia doza amlodipina sostavila 5 mg, dlitel'nost' priema 12 nedel'. Metody kontrolia vkliuchali obshcheklinicheskie metody obsledovaniia, ofisnoe izmerenie i sutochnoe monitorirovanie arterial'nogo davleniia (SMAD), otsenku perenosimosti i genotipirovanie po polimorfnomu markeru S3435T gena AVSV1 metodom PTsR-PDRF (polimeraznaia tsepnaia reaktsiia i polimorfizm dlin restriktsionnykh fragmentov). Statisticheskaia obrabotka rezul'tatov provodilas' s ispol'zovaniem U-kriteriia Manna-Uitni dlia kolichestvennykh peremennykh, odnomernyĭ (odnofaktornyĭ) dispersionnyĭ analiz Kruskala-Uollisa (ANOVA) – dlia trekh nezavisimykh grupp kolichestvennykh dannykh. Otlichnaia antigipertenzivnaia éffektivnost' u bol'nykh s genotipom SS sostavila 11,8%, ST – 33,9%, TT - 43,3%; khoroshaia – 35,3%, 32,1% i 33,3% sootvetstvenno, udovletvoritel'naia – 52,9%, 34,0% i 23,4% sootvetstvenno. Uvelichenie dozy do 10 mg potrebovalos' 6-ti bol'nym s genotipom ST i 9-ti bol'nym s genotipom SS. Kolichestvo bol'nykh s NPR pri genotipe SS sostavilo 35,3%, TT – 6,7%, ST – 11,3%. Po rezul'tatam mnogofaktornogo analiza ANOVA vyiavleny dostovernye razlichiia mezhdu genotipami CC i TT po stepeni snizheniia SAD (r=0,02), pokazateliu antigipertenzivnoĭ éffektivnosti (r=0,02), potrebnosti v uvelichenii dozy (r=0,04) i chastote razvitiia NPR (r=0,05). U bol'nykh AG I-II stepeni s genotipom TT po polimorfnomu markeru S3435T gena mozhno ozhidat' bolee vysokikh pokazateleĭ antigipertenzivnoĭ éffektivnosti amlodipina v sochetanii s khoroshim profilem bezopasnosti i naibolee nizkim protsentom razvitiia NPR, a u bol'nykh s genotipom SS vyshe veroiatnost' razvitiia NPR na fone bolee nizkoĭ antigipertenzivnoĭ éffektivnosti.
Keywords: ABCB1 gene; amlodipine; arterial hypertension; gene polymorphism; pharmacogenetics.