The role of risk factors and genetic polymorphism in assessing the effectiveness of combined antihypertensive therapy in a small population of shor people

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According to the latest Russian guidelines for arterial hypertension (AH), the first choice drugs include combinations of blockers of the renin-angiotensin-aldosterone system (RAAS) with calcium antagonists (CA) or with thiazide / thiazide-like diuretics. However, in some patients despite the introduction of more and more advanced drugs for the treatment of hypertension into clinical practice it is not possible to achieve the target level of blood pressure. In this regard a number of authors propose to prescribe antihypertensive drugs taking into account the role of gene polymorphism. In addition, there are racial differences in drug tolerance and efficacy.

OBJECTIVE

To assess the role of traditional risk factors and genetic markers in the effectiveness of combined antihypertensive therapy in the indigenous population of Mountain Shoria.

MATERIAL AND METHODS

In 2013—2017 the indigenous small-numbered population, the Shors, was surveyed by a continuous method in the villages of Mountain Shoria. The prospective observation included 320 patients with hypertension who had not previously received antihypertensive therapy. The subjects were randomized by the method of plain envelopes into two groups of 160 patients each. In group 1 the patients were prescribed initial therapy with a combination of RAAS blockers with CA; in group 2 the patients received a combination of RAAS blockers with a thiazide-like diuretic. The study of molecular genetic parameters included: DNA isolation from venous blood by phenol-chloroform extraction, determination by PCR of single nucleotide polymorphisms: ACE (I/D, rs 4340), AGT (c.803T>C, rs699), AGTR1 (A1166C, rs5186), MTHFR (C677T, rs1801133), eNOS (VNTR 4b/4a).

RESULTS

A prospective observation in Mountain Shoria demonstrated the same antihypertensive efficacy of both drug combinations. However, in comorbid pathology (hypertension and concomitant obesity or impaired carbohydrate metabolism) the combination of RAAS blockers with a diuretic was more effective. In Shors a pronounced hypotensive effect using a combination of RAAS blockers with CA was established for carriers of genotypes I/D of the ACE gene, genotypes T/C of the AGT gene, genotypes C/C of the AGTR1 gene. The presence of various cardiovascular risk factors in addition to hypertension in patients did not reduce the positive result of treatment. The polymorphism of the MTHFR and eNOS genes in the Shors determined a more significant dynamics of blood pressure in case of antihypertensive therapy with RAAS blockers and diuretic, in persons with impaired carbohydrate metabolism and obesity, accordingly.

CONCLUSION

Personalized medicine which studies the genetic basis of an individual response to drugs opens up new opportunities in the treatment of patients with hypertension and is aimed at increasing the effectiveness of therapy.

Keywords:

antihypertensive therapy

the role of gene polymorphism

personalized medicine

ethnicity

Authors:

Mulerova T.A.

Research Institute for Complex Issues of Cardiovascular Diseases

Tsygankova D.P.

Research Institute for Complex Issues of Cardiovascular Diseases

Chigisova A.N.

Research Institute for Complex Issues of Cardiovascular Diseases

Ogarkov M.Yu.

Research Institute for Complex Issues of Cardiovascular Diseases

Received:

07.06.2020

Accepted:

23.11.2020

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