Evaluation of the relationship between the minimum steady-state concentration of angiotensin II receptor blockers and polymorphic markers of CYP2C9 (Arg144Cys), CYP2C9 (IlE359Leu), AGTR1 (A1166C), AGT (Met235Thr, C4072T), ACE (I/D), CYP11B2 (C-344T) genes and office arterial pressure

The aim of the work was to study the relationship of the minimum steady-state concentration of angiotensin II receptor blockers with polymorphic markers of CYP2C9 (Arg144Cys), CYP2C9 (Ile359Leu), AGTR1 (A1166C), AGT (Met235Thr, C4072T), ACE (I/D), CYP11B2 (C-344T) genes and the office blood pressure (BP) indices.

Materials and methods. The study included 179 patients of the Moscow region with newly diagnosed hypertension of stages 1–2, among whom there were 141 (78.8%) women and 38 (21.2%) men aged from 32 to 69 years (mean age — 58.2±6.4, median age — 60 (57–63 years), who had been randomized into treatment groups with valsartan and irbesartan in the form of mono- or combination therapy with hydrochlorothiazide. After 3 weeks of pharmacotherapy, polymorphic markers CYP2C9 (Arg144Cys), CYP2C9 (Ile359Leu), AGTR1 (A1166C), AGT (Met235Thr, C4072T), ACE (I/D), CYP11B2 (C-344T) were genotyped and the minimum steady-state concentrations of irbesartan and valsartan were determined. The office BP measurements were performed on each visit.

Results. The carriers of alleles *2 and *3 of the CYP2C9 gene, the genotype T/T of the AGT gene, the genotype I/I of the ACE I/D polymorphism achieved higher values of the minimum steady-state concentration of irbesartan after 3 weeks of pharmacotherapy. Homozygotes A/A for the genetic polymorphism of the AGTR1 gene (A1166C), homozygotes D/D for the ACE I/D polymorphism reached significantly higher values of the minimum-steady concentration of valsartan after 3 weeks of pharmacotherapy. In the patients taking irbesartan, a more pronounced decrease in the office systolic (SBP) and diastolic (DBP) BP was detected with an increase in the concentration for every 100 ng/mL after 3 weeks of therapy. Any association of the indicators with the valsartan concentration was found out.

Conclusion. The effects of irbesartan and valsartan indicate a maximum modulation of pharmacodynamic effects during 3 weeks of pharmacotherapy, followed by a consolidation in the therapeutic range and a stop in the increasing the effectiveness with a further increase in the steady-state concentration, which can be used to predict therapy, personalize it, a better control and a high safety profile.

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