Effect of C-344T polymorphism of aldosterone synthase gene on variability of antihypertensive therapy with angiotensin II receptor blockers: open randomized controlled clinical trial

The effectiveness of the antihypertensive therapy may be associated with genetic factors that affect not only the degree of a blood pressure elevation but also predetermine an interindividual variability in response to the antihypertensive treatment.

The aim of the work was to study pharmacodynamic indices of the effectiveness of therapy with angiotensin II receptor blockers (ARBs) in the form of monotherapy and as a part of combined drugs in patients with an arterial hypertension (AH) depending on genetic features of patients – a polymorphism of the gene encoding aldosterone synthase, the C-344T polymorphism.

Materials and methods. The study included 179 patients of the Moscow region with a newly diagnosed 1–2-degree AH (141 (78.8%) women and 38 (21.2%) men) aged from 32 to 69 years who had been randomly allocated to treatment groups with irbesartan and valsartan in the form of the mono- or combined therapy with hydrochlorthiazide by simple randomization. After 3 weeks of pharmacotherapy, the presence of the genetic rs1799998 (C-344T) polymorphism of the aldosterone synthase gene, CYP11B2, and the minimum equilibrium concentration of angiotensin receptor blockers (ARBs) were determined.

Results. TT homozygotes in the irbesartan group were characterized by a lower level of the blood pressure (BP) target achievement after 3 weeks of pharmacotherapy and a higher frequency of the need to intensify the antihypertensive therapy compared with CT and TT genotypes. Among the patients taking valsartan, the carriers of the TT genotype were characterized by a higher frequency of achieving the target BP after 3 weeks of pharmacotherapy compared to the CC (p <0.001) and CT genotypes (p=0.084). Herewith, at the end of the study, according to the results of the office BP measurement and daily BP monitoring (DBPM), the achievement of the target BP values was not significantly associated with CYP11B2 C-344T genotype in both irbesartan (p >0.999) and valsartan (p=0.149). There was a trend toward a slightly more pronounced decrease in the daytime HR in the heterozygotes receiving irbesartan by a mean of 1.9 bpm compared to the CC homozygotes (p=0.059). The CT heterozygotes taking valsartan, were characterized by a less pronounced decrease in the HR by a mean of 1.4 bpm compared to the TT homozygotes (p=0.045). Moreover, the minimum drug concentration was not a statistically significant mediator of the effects (p=0.484 and p=0.736, respectively).

Conclusion. When personalizing the AH therapy in the patients of the Moscow region, to optimize the achievement of the target BP, the carriers of the TT genotype C-344T on the CYP11B2 gene should be recommend valsartan as the starting therapy of ARBs in the form of the mono- or bicomponent therapy depending on the AH degree.

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