Features of antihypertensive and vasoprotective efficiency of combination of valsartan and amlodipine in patients with obesity under different polymorphic variants of CYP2C9 and CYP11B2 genes

Purpose. To evaluate the efficiency of combination antihypertensive therapy with valsartan and amlodipine in patients with arterial hypertension (AH) and obesity, depending on the polymorphisms of the CYP2C9 and CYP11B2 genes. Materials and methods. In research included 80 obese patients (body mass index ≥30 kg/m2) and AH 1-2 disease blood pressure (BP) ≥140/90 mm Hg and <180/110 mm Hg against the background of previous antihypertensive therapy) uncontrolled medication. The patients included in the research received a fixed combination of valsartan and amlodipine at doses of 80-160/5-10 mg/day. All patients were measured office BP, implementambulatory blood pressure monitoring (ABPM) with the definition of central aortic systolic pressure (CASP) and stiffness indicators vascular wall at baseline and after 16 weeks of therapy. Venous blood samples were taken from all patients, followed by DNA extraction from leukocytes by the method of phenol-chloroform extraction. Determination of polymorphic variants of the researched genes was performed by amplification in real time on the amplifier Rotor Gene Q. We used sets of primers and probes (“Sintol”, Russia) and the Taq Man method (allele discrimination). Results. It was shown that patients with *1/*2 and *1/*3 variants more often reached the target level of office BP than with polymorphism *1/*1 (respectively 92.8 and 90.1% vs 43.7% cases, p<0.05). At the same time, in patients with polymorphisms *1/*2 and *1/*3 compared with persons who had the option *1/*1, a more expressed decrease in most indicators of ABPM and positive changes in the CASP and stiffness of the vascular wall (p<0.05) were found. When analyzing the effeciency of treatment with regard to polymorphic variants of the CYP11B2 gene, significantly more frequent achievement of the target level of BP was observed with mutant polymorphism *2/*2, than with polymorphism *1/*2 (76.5% vs 50%). When comparing the degree of change in ABPM, CASP, and vascular wall stiffness, depending on the polymorphic variant of the CYP11B2 gene, a more pronounced positive dynamics of most parameters in polymorphism carriers *2/*2 was found than in persons with *1/*1 and *1/*2. It was also found that among persons with the most frequent polymorphism of the CYP2C9 gene - *1/*1, reached the target level of BP as a result of 16-week therapy, there was a significant predominance of the polymorphism *2/*2 of the CYP11B2 gene over its other variants. Conclusion. Obtained during our study data on the relationship of the effectiveness of therapy with valsartan and amlodipine with different polymorphisms of the CYP2C9 and CYP11B2 genes can be used and taken in to account in the individualized selection of antihypertensive therapy patients with AH and concomitant obesity. It can also be assumed that genetic testing preceding the correction of treatment, as one of its personalization options, will help increase the effectiveness of pharmacotherapy in patients with AH and obesity

arterial hypertension, obesity, gene polymorphic variants, CYP2C9 gene, CYP11B2 gene, combined antihypertensive therapy

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