The effect of A1166C polymorphism of the type 1 angiotensin II receptor gene (AGTR1) on the dynamics of blood pressure during therapy with angiotensin II receptor blockers: a randomized prospective clinical trial

Background. More and more data confirm the need for personalized pharmacotherapeutic treatment based on the genetic characteristics of the patient, which will become the main method of future antihypertensive treatment, especially in patients with refractory hypertension, in order to rationally prescribe pharmacotherapy.

Aims — to study the pharmacodynamic parameters of the effectiveness of therapy with angiotensin II receptor blockers in the form of monotherapy and as part of combined drugs in patients with hypertension, depending on the genetic characteristics of patients – the genetic polymorphism A1166C of the angiotensin II type 1 receptor gene (AGTR1). Methods. The study included 179 patients from the Moscow region with newly diagnosed arterial hypertension (AH) of 1–2 degrees, among whom 141 (78.8%) women and 38 (21.2%) men aged 32 to 69 years, who were randomly assigned to irbesartan and valsartan groups in the form of mono- or combination therapy with hydrochlorothiazide by a simple randomization method. After 3 weeks of pharmacotherapy, the presence of the rs5186 (A1166C) genetic polymorphism of the type 1 angiotensin II receptor gene (AGTR1) was determined.

Results. After 3 months of valsartan therapy, among heterozygotes, the change in office DBP was statistically significantly less pronounced compared to the A/A genotype by an average of 5.4 mmHg (p = 0.009), and there was also a less pronounced decrease by an average of 5.6 mmHg, however, not statistically significant, in heterozygotes compared to the C/C genotype (p = 0.192). There was a tendency in patients with genotype A/C compared with genotype A/A after 3 weeks of using irbesartan in the form of a less pronounced decrease in office SAD by an average of 4.3 mmHg. The decrease in office DBP was less pronounced by an average of 5.2 mmHg (p = 0.019); patients with CC genotype also showed a less pronounced decrease in DBP (by an average of 4.2 mmHg), compared with the A/A genotype, however, this difference was not statistically significant (p = 0.48).

Conclusions. The A1166C polymorphism of the AGTR1 gene significantly affects the antihypertensive effect of valsartan in patients with grade 1–2 hypertension, leading to a decrease in DBP and an increase in HR in A/C heterozygotes compared to A/A homozygotes. No association between the polymorphism and the antihypertensive effect of irbesartan was identified; however, patients with A/C and C/C genotypes showed a less pronounced reduction in SBP and DBP. No relationship was found between genotype and the achievement of target BP levels or the need for therapy intensification. Further prospective studies with a larger sample size are required to clarify the genetic factors influencing the antihypertensive efficacy of ARBs.