Цель. Исследование ассоциации A1166/166C полиморфизмов гена сосудис-того рецептора 1 типа ангиотензина II (AGT2R1) с развитием коронарного и периферического атеросклероза в этнических группах населения Респу-блики Адыгея. Материал и методы. Распределение A1166/166C полиморфных вариантов гена AGT2R1 исследовано "single nucleotide polymorphism" (SNP) -методом с аллель-специфическими праймерами и электрофоретической детекцией результатов (НПФ "Литех"). Полиморфизмы гена AGT2R1 (rs5186) с нуклео-тидной заменой аденина на цитозин (А>C) в 1166 позиции гена AGT2R1 типи-рованы в образцах геномной ДНК доноров (n=143) и больных с сердечно-сосу-дистыми заболеваниями (n=39) в возрасте 23-65 лет из двух этнических групп -адыгов и русских. Экспериментальные данные проанализированы адекватными статистическими методами SPSS Statistics 17.0. Результаты. В группе больных с осложнениями коронарного и перифериче-ского атеросклероза выявлено статистически значимое повышение частоты мутантной 1166С аллели и патологического гомозиготного генотипа С1166С. Риск развития сердечно-сосудистых заболеваний у носителей 1166С аллеля возрастает в 3,77 раз (c 2 =26,07; р=0,00003), а в случае с гомозиготным "мутантным" СС генотипом -в 10,36 раз (c 2 =31,20; р=0,00002), что позволяет использовать 1166C аллель и С1166С генотип AGT2R1 в качестве генетических предикторов коронарного атеросклероза и маркеров донозологической диа-гностики ишемической болезни сердца (c 2 =42,96; р=0,0000005; OR (95%)=17,37). Заключение. Полученные экспериментальные данные в сочетании с допол-нительными инструментальными исследованиями функционального состоя-ния сердечно-сосудистой системы, будут способствовать улучшению точно-сти диагностики атеросклероза и возможных осложнений последнего на ран-них этапах, что позволит снизить инвалидизацию и смертность среди лиц трудоспособного возраста. Aim. The investigation of A1166/166C polymorphisms of the vascular receptor 1 type of angiotensine II gene (AGT2R1) association with the development of coronary and peripheral atherosclerosis in ethnic groups of Adyghea Republic inhabitants. Material and methods. The spread of A1166/166C polymorphic variants of the gene AGT2R1 was studied via the "single nucleotide polymorphism" (SNP) -method with allele-specific primers and electrophoretic results detection (by SPF "Litech"). Gene polymorphisms AGT2R1 (rs5186) with nucleotide replacement of adenine by cytosine (А>C) in the 1166th position of gene AGT2R1 were typified in the samples of donors genomic DNA (n=143) and of those with cardiovascular diseases (n=39) at the age 23-65 y. o. from two ethnic subgroups -Adyghes and Russians. The data was processed via software SPSS Statistics 17.0. Results. In the group of those with complicated coronary and peripheral atherosclerosis there was statistically significant increase of the prevalence of mutant 1166C allele and of pathological monozygous genotype C1166C. The risk of cardiovascular diseases in the carriers of 1166C allele increases 3,77 times (c 2 =26,07; р=0,00003), and in the case ...

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Understanding the pathogenetic mechanism of development and identifying trigger markers of the disease will significantly increase the efficiency of pre-nosological diagnosis and medical follow-up of patients. In this case, one should take into account the role of mutations in cytokine genes, which affect their biochemical activity and production level. The objective of the study was to investigate the role of mediators of acute and chronic inflammation (IL-17A, IL-1â, TNFá and IL-4), the ratio of natural killer cell subpopulations (CD56hiCD16-/CD56loCD16+) in pathogenesis of coronary atherosclerosis resulting into coronary heart disease.To analyze the results, an integrated approach was used, including molecular genetic methods such as polymerase chain reaction, typing of single-nucleotide substitutions in cytokine genes, isolation and cultivation of peripheral blood mononuclear cells, assessment of spontaneous and in vitro-induced production of immune system mediators, enzyme-linked immunosorbent assay, cytotoxic test, flow cytometry with monoclonal antibodies (Beckman Coulter, USA) to CD16, CD56 NK markers.The study included 130 residents of the North Caucasus, including the patients (n = 62) treated at the Cardiology Department of the Adyghe Republican Clinical Hospital (ARCB) with a verified diagnosis of ischemic heart disease (IHD), and a control group (n = 68), represented by unrelated healthy donors.Overexpression of cytokines in IHD patients was associated with distinct single nucleotide substitutions in certain genes. Studying a group of residents from the Republic of Adygeya, the authors experimentally established that harboring the 511C allele of the IL-1â gene (p < 0.0004; OR = 4.67), A197A of the IL-17A gene genotype (p < 0.04; OR = 3.88), G308 SNP of TNFá gene (p < 0.01; OR = 3.41), and 589T variant of IL-4 gene (p < 0.04; OR = 2.45) are associated with hyperproduction of the first-wave inflammatory mediators that increase the risk of developing ischemic heart disease. In atherosclerosis and associated cardiovascular diseases, we have noted a significant decrease in spontaneous and induced activity of natural killer cells involved in the utilization of “foamy cells”. The NK activity of peripheral blood mononuclear cell in patients with coronary heart disease is significantly reduced. In the IHD patients, an imbalance of phenotypically and functionally different CD56hiCD16-/CD56loCD16+ NK subpopulations with a predominance of CD56hiCD16- phenotype were revealed. Conclusions: Immuno-inflammatory mechanisms of evolving coronary atherosclerosis are associated with single-nucleotide substitutions, i.e., polymorphisms in the promoter regions of the IL-17A (G197A), IL-1 â (T511C), and TNFá (G308A), the known mediators of acute and chronic inflammation.Genetically determined overexpression of IL-17A, IL-1â, and TNFá, confirmed in experiments on evaluation of spontaneous and stimulated cytokine production in patients with CHD, together with reduced NK activity of РВМС, due to predominance of CD56hiCD16-, a subpopulation with high cytokine production, manifested by an increased pro-inflammatory component that triggers and provides long-term support to pathophysiological processes of atherosclerosis.

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