The effect of polymorphism of the angiotensin-converting enzyme gene on the course of arterial hypertension in combination with type 2 diabetes and the effectiveness of antihypertensive therapy
DOI:
https://doi.org/10.14739/2310-1237.2024.2.299579Keywords:
single nucleotide polymorphism, angiotensin-converting enzyme, arterial hypertension, type 2 diabetes, antihypertensive therapyAbstract
The aim of the work is to determine the influence of angiotensin-converting enzyme (ACE) gene polymorphism on the course and effectiveness of antihypertensive therapy using the ACE inhibitor lisinopril and the beta-blocker carvedilol in patients with comorbidity of arterial hypertension and type 2 diabetes.
Materials and methods. The study was carried out based on the Department of arterial hypertension and kidney disease of the L. T. Malaya Therapy National Institute of the National Academy of Medical Sciences of Ukraine. The study included 106 patients with arterial hypertension of the 2nd degree, stage II and diabetes mellitus type 2, the average age was 54.3 ± 5.3 years. All patients were divided into three groups. The first group consisted of 48 patients with the A/A genotype of the polymorphic marker 2350 A/G of the angiotensin-converting enzyme gene, the second group included 22 patients with the A/G genotype, and the third group included 36 patients with the G/G genotype. DNA of peripheral blood leukocytes was used to study the single-nucleotide polymorphism of marker 2350 A/G of the angiotensin-converting enzyme gene. A combination of lisinopril and carvedilol was used as antihypertensive therapy.
Results. Direct correlations were established between the presence of A/G and G/G genotypes of the single-nucleotide polymorphism 2350 A/G of the angiotensin-converting enzyme gene with an increased body mass index (p < 0.001), higher levels of systolic and diastolic blood pressure (p < 0.001), with an increased level of fasting blood glucose (p < 0.05), the HOMA-IR (p < 0.05), an increased level of low-density lipoproteins (p < 0.05) and triglycerides of the blood (p < 0.05). Positive correlations of the specified polymorphisms with an increase in the mass index of the myocardium of the left ventricle were also established (p < 0.001). As a result of the treatment, a significant decrease in blood pressure, both systolic and diastolic, was observed in all patients (p < 0.001). A statistically significant decrease in the left ventricular myocardial mass index was found (p < 0.001) in all groups of patients. At the same time, the reduction of left ventricular myocardial hypertrophy was statistically more pronounced in patients with genotype A/A than in patients with genotypes A/G and G/G (p < 0.05). In three groups of patients, a significant (p < 0.05) decrease in BMI was observed under the influence of diet therapy and drug treatment. Among the comparison groups of patients, the statistically most significant decrease of this indicator in treatment dynamics was found in individuals with the A/A genotype. A significant decrease in fasting blood glucose levels, HOMA-IR insulin resistance index, and markers of atherogenic dyslipidemia was revealed in both patients with the A/A genotype and those with the A/G and G/G genotypes (p < 0.05). The decrease in the level of insulin resistance (IR) in patients after treatment in all studied groups had positive correlations with the decrease in indicators of left ventricular hypertrophy (LVH) (p < 0.05). Positive correlations were also observed in patients of all observation groups between a decrease in body mass index (BMI) after treatment and a decrease in LVH (p < 0.05). There were no statistically significant differences between the studied parameters between the A/G and G/G groups, both before and after treatment. This confirms that the G allele of the polymorphic marker 2350 A/G of the ACE gene is associated with the development of hypertension and LVH.
Conclusions. The therapy with the combination of lisinopril and carvedilol in patients with hypertension and type 2 diabetes contributed to the effective reduction of blood pressure in three groups of patients. It was established that patients with genotypes A/G and G/G of the polymorphic marker 2350 A/G of the ACE gene had more pronounced hypertrophic changes of the myocardium than patients with genotype A/A before the start of treatment. Antihypertensive therapy was the most effective in reducing myocardial hypertrophy in patients with the A/A genotype of the polymorphic marker 2350 A/G of the ACE gene. It was found that the presence of genotypes A/G and G/G of the polymorphic marker 2350 A/G of the ACE gene can be used as a predictor not only of the development of LVH but also of metabolic disorders associated with increased BMI, glycemia and insulin resistance, expressed by shifts in atherogenic dyslipidemia in patients with comorbid hypertension and type 2 diabetes. It was established that a decrease in the degree of LVH accompanied by a decrease in IR and BMI. It has been proven that the use of antihypertensive therapy with the use of carvedilol and lisinopril in the treatment regimen in patients with unfavourable genotypes A/G and G/G of the polymorphic marker 2350 A/G of the ACE gene is effective and contributes to marked regression of LVH. It was determined that patients with the AA genotype of the polymorphic marker 2350 A/G of the ACE gene have the greatest prerequisite for the effective reduction of LVH after treatment, which was considered a favourable prognostic sign.
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