Correlation between CYP2C9 polymorphisms and office blood pressure levels in patients treated with irbesartan and valsartan

Arterial hypertension (AH) is one of the most significant modifiable risk factors for cardiovascular diseases, affecting approximately 1.5 billion people worldwide. The study of genetic polymorphisms involved in blood pressure regulation is a promising direction for elucidating the molecular and biological mechanisms underlying the pathogenesis of hypertension. Analyzing associations between gene variants and the response to antihypertensive therapy offers opportunities to develop personalized treatment strategies aimed at improving the efficacy and safety of pharmacotherapy. Objective. To evaluate the pharmacodynamic efficacy of angiotensin II receptor blockers (ARBs), used as monotherapy or in combination with hydrochlorothiazide, in patients with newly diagnosed AH depending on their genetic background, specifically the CYP2C9 gene polymorphisms Arg144Cys(rs1799853, CYP2C9*2) and Ile359Leu (rs1057910, CYP2C9*3). Materials and methods. The study included 179 patients from the Moscow region with newly diagnosed grade 1–2 arterial hypertension, comprising 141 (78.8 %) women and 38 (21.2 %) men aged 32 to 69 years. Participants were randomly assigned to receive either irbesartan or valsartan as monotherapy or in combination with hydrochlorothiazide using simple randomization. Venous blood samples for genotyping CYP2C9*2 and *3 polymorphisms were collected three weeks after enrollment. Office blood pressure was measured at baseline, at 3 weeks, and at 3 months of therapy. Results. In patients with newly diagnosed AH who had not previously received antihypertensive treatment, a comparative analysis of the effectiveness of irbesartan and valsartan was performed based on CYP2C9*2 (Arg144Cys) and CYP2C9*3 (Ile359Leu) genotypes. Carriers of the *2 and *3 alleles showed a more pronounced reduction in office systolic and diastolic blood pressure after three weeks of therapy with both irbesartan and valsartan. However, by the end of the 3-month follow-up, no statistically significant association was observed between genotype and the magnitude of the antihypertensive response. The influence of CYP2C9 polymorphisms on heart rate was limited and mostly did not reach statistical significance. Conclusion. The findings suggest a potential role for pharmacogenetic testing in the initiation of angiotensin II receptor blocker therapy in patients with newly diagnosed arterial hypertension.