Role of ACE gene polymorphism (RS4646994) in the pathogenesis of arterial hypertension formation in person performing task in the Arctic region

The results of content analysis of the role of polymorphism of the ACE gene genotype (RS4646994) in persons employed in the Arctic region are presented. It has been shown that it can be recommended as a universal marker in the diagnosis of not only essential hypertension, but other diseases of the cardiovascular system. In order to reduce the risk of developing pathological conditions, when planning official activities in the Arctic region, it is advisable to build professional selection, taking into account not only their genetic predisposition, but also the body's ability to maintain homeostasis. Key words: Arctic, polymorphism, ACE gene (RS4646994), arterial hypertension, homeostasis.

ASSOCIATION OF BDKRB2 AND ACE GENE POLYMORPHISM WITH ERYTHROCYTE ADRENOREACTIVITY IN YOUNG MEN WITH DIFFERENT MOTOR ACTIVITY

The aim of the paper was to study the association of polymorphic variants of rs4646994 (I/D) of the angiotensin converting enzyme gene (ACE) and rs5810761 (+9/-9) of the bradykinin B2 receptor gene (BDKRB2) with erythrocyte adrenoreactivity (ARE) in athletes and untrained young men. Materials and Methods. The study involved 61 young men (aged 21–23) with different levels of motor activity (MA). ARE was evaluated according to the erythrocyte sedimentation rate (ESR) change under adrenaline in vitro at final concentrations 10-5, 10-6, 10-7, 10-9, 10-11, 10-13 g/ml of venous blood. According to the effect observed and ESR shifts under adrenaline, we distinguished 3 ARE types: antiaggregative (AnAg), areactive (Ar) and aggregative (Ar). Results. The results of comparative and correlation analyses demonstrated that young athletes with +9/-9 (BDKRB2) genotype were characterized by a higher aggregative resistance of erythrocytes to the effects of both physiological (<10-9 g/ml) (physiological adrenaline concentration, PAC) and stressful doses (>10-9 g/ml) of adrenaline (stress adrenaline concentration, SAC), as well as by predominance of AnAg and Ar ARE types. In athletes, among the representatives of different genotypes of АСЕ gene I/D polymorphism, the erythrocyte response to adrenaline did not have any statistically significant differences. In physically inactive students, namely individuals with the D/D genotype, maximal ESR deviation under PAC was less than in those with I/D genotype. Conclusion. Athletes with *-9 allele (+9/-9 genotype) in their genotype can be considered more stress-resistant, which is provided by optimal adaptive and compensatory body mechanisms. Apparently, resistance of cells to the adrenaline contributes much to the work of these mechanisms. As for the ACE gene polymorphism, its effect on the suspension characteristics of erythrocytes is less pronounced not only in physically inactive young men, but in athletes as well. Keywords: erythrocyte adrenoreactivity (ARE), stress tolerance, β2 bradykinin receptor gene (BDKRB2), angiotensin converting enzyme (ACE) gene, motor activity. Цель работы – изучить ассоциацию полиморфных вариантов rs4646994 (I/D) гена ангиотензинпревращающего фермента (АСЕ) и rs5810761 (+9/-9) гена рецептора брадикинина 2 типа (BDKRB2) с адренореактивностью эритроцитов (АРЭ) у спортсменов и юношей, ведущих физически малоактивный образ жизни. Материалы и методы. В исследовании принял участие 61 юноша с разным уровнем двигательной активности (ДА) в возрасте 21–23 лет. Оценку АРЭ проводили по изменению скорости оседания эритроцитов (СОЭ) под действием адреналина in vitro в конечных концентрациях 10-5, 10-6, 10-7, 10-8, 10-9, 10-11, 10-13 г/мл венозной крови. По характеру наблюдаемого эффекта в соответствии с направленностью сдвигов СОЭ в присутствии адреналина мы выделили 3 типа АРЭ: антиагрегационный (АнАг), ареактивный (Ар) и агрегационный (Аг). Результаты. По результатам сравнительного и корреляционного анализа установлено, что юноши-спортсмены с генотипом +9/-9 (BDKRB2) характеризуются более высокой агрегативной устойчивостью эритроцитов к воздействию как физиологических (10-9 г/мл и ниже), так и повышенных (стрессовых) доз (выше 10-8 г/мл крови) адреналина, а также преобладанием АнАг- и Ар-типов АРЭ. У представителей разных генотипов полиморфизма I/D гена АСЕ реакция эритроцитов на адреналин не имела статистически значимых различий в группе спортсменов, тогда как в группе малоактивных студентов у лиц с генотипом D/D максимальное отклонение СОЭ при ФКА было меньше, чем при генотипе I/D. Выводы. Спортсменов, имеющих в своём генотипе аллель *-9 (+9/-9 генотип), можно считать более стрессоустойчивыми, что обеспечивается оптимальными адаптивно-компенсаторными механизмами организма, существенная роль в обеспечении которых, по-видимому, принадлежит устойчивости клеток к действию адреналина. Что касается полиморфизма гена АСЕ, то его влияние на суспензионные характеристики эритроцитов выражено слабее не только у физически малоактивных юношей, но и у спортсменов. Ключевые слова: адренореактивность эритроцитов (АРЭ), стрессоустойчивость, ген рецептора брадикинина β2 (BDKRB2), ген ангиотензинпревращающего фермента (АСЕ), двигательная активность.

Correlation of ACE Gene Polymorphism and Hypertension in Stroke Ischemic Patients

Stroke is the third highest cerebrovascular disease in the world with high mortality and disability rate that is mostly dominated by ischemic stroke. Genetic factor that had been reported to have an indirect effect in increasing the incidence of ischemic stroke is ACE gene polymorphism. ACE gene polymorphism is characterized by the insertion marked by letter (I) or deletion marked by letter (D) on intron 16, chromosome 17. ACE gene polymorphism has drawn a lot of attention from scientists and had been reported to have an indirect effect in increasing the ischemic stroke incidence through pathogenesis of hypertension and atherosclerosis. In this study, 78 subjects of ischemic stroke consist of 43 subjects with hypertension and 35 subjects with normotension. I allele of ACE gene polymorphism was more dominant than D allele in hypertensive ischemic stroke patients (72.1% > 27,9%) and this dominance was also seen in the incidence of hypertension vs normotension (55.4% > 44.6%). However, the correlation of ACE gene polymorphism with the incidence of hypertension was not statistically significant when compared based on its genotype (p=0.280) and allele (p=0.948).

Angiotensin Converting Enzyme Gene Insertion/Deletion Polymorphism Is Not Responsible for Antihypertensive Therapy Induced New Onset of Type 2 Diabetes in Essential Hypertension

Background: Antihypertensive drug therapies have been reported to be associated with new onset of type 2 diabetes mellitus in some hypertensive patients after prolonged use. Angiotensin converting enzyme (ACE) gene has been found to affect essential hypertension, response of antihypertensive therapies, and glycemic disturbances. Therefore, ACE gene I/D polymorphism may be associated with risk of new onset of type 2 diabetes via metabolic disturbances, glycemic dysregulation, and insulin resistance. Aim: To assess the correlation between ACE gene I/D polymorphism and glycemic disturbance under influence of diuretic and other antihypertensive drug therapies. Materials and methods: We recruited 270 normotensive patients as control (150 men and 120 women), 270 hypertensive patients (95 men and 175 women), and 240 hypertensive with new onset of diabetes patients (80 men and 160 women). All samples were genotyped for ACE gene polymorphic alleles and relationship between different genotypes and anthropometric and clinical parameters along with drug therapies was established and analyzed. Results: Baseline clinical (systolic blood pressure, diastolic blood pressure, and fasting blood glucose level) and anthropometric parameters (height, weight, waist circumference, hip circumference, waist-hip ratio, and body mass index) of study populations were found highly statistically significant ( P < .05) when compared among study groups. Furthermore, genotype wise comparison of all these parameters in essential hypertensive (EH) and essential hypertensive with onset of diabetes (EHNOD) patients found most of them nonsignificant and no variation was found with respect to different genotypes of ACE gene. The genotype wise comparison of clinical parameters among different antihypertensive drug therapy was found statistically nonsignificant in both EH and EHNOD patients. Discussion: Anthropometric parameters can be taken as the risk indicator factors for hypertension and diabetes. However, ACE gene polymorphism may not be a risk factor for development of diabetes in hypertensive patients. Conclusion: The present study suggested that ACE gene polymorphism did not show any significant association with the risk of new onset of diabetes in EH patients and more detailed studies with large population size are needed. [Formula: see text]