Assessing the influence of the angiotensinogen gene’s polymorphic marker M235T on the changes in daily blood pressure monitoring indicators in patients with stage I–II hypertension

Abstract

BACKGROUND: The effectiveness of antihypertensive therapy may be associated with genetic factors that both influence the degree of increase in blood pressure and determine inter-subject variability of response to antihypertensive treatment.

AIM: To study pharmacodynamic parameters of the effectiveness of therapy with angiotensin II receptor blockers as monotherapy and as part of combination drugs in patients with hypertension, depending on the genetic characteristics of patients, specifically the M235T polymorphism of the angiotensinogen gene.

MATERIALS AND METHODS: The study involved 179 patients from the Moscow region with newly diagnosed stage I–II hypertension, including 141 (78.8%) women and 38 (21.2%) men aged 32 to 69 years, who were randomly assigned to groups receiving irbesartan and valsartan as monotherapy or in combination therapy with hydrochlorothiazide, using a simple randomization method. Genetic polymorphism rs699 (C4072T, M235T) of the AGT angiotensinogen gene was determined after 3 weeks of drug therapy.

RESULTS: After three months of drug therapy, the maximum antihypertensive effect in the group of patients receiving valsartan was observed in CC homozygotes and heterozygotes by the level of decrease in mean daytime systolic blood pressure. In CC homozygotes, a trend was outlined by the level of decrease in mean daytime diastolic blood pressure; in CC homozygotes, by the level of decrease in mean nighttime systolic blood pressure; in CC and TT homozygotes, by the level of decrease in mean nighttime diastolic blood pressure. No statistically significant association of the angiotensinogen gene’s M235T polymorphism genotype with these parameters was found among patients receiving irbesartan.

CONCLUSIONS: The obtained data may indicate a more rapid and stable antihypertensive effect in patients carrying the C allele of the M235T genetic polymorphism of the angiotensinogen gene. Therefore, personalized therapy of arterial hypertension using the detection of the M235T genetic polymorphism in the AGT gene may reasonably include the AT1-receptor blocker valsartan as a starting therapy for the C allele carriers in the Moscow region, as monotherapy or two-component therapy, depending on the stage of hypertension.

Keywords

hypertension / angiotensinogen gene / AGT / M235T polymorphism / irbesartan / valsartan

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