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DOI 10.26724/2079-8334-2019-1-67-88 UDC 616.12-008.44-085.22:576.8.095.52
POLYMORPHISM OF C825T (RS5443) G-PROTEIN Pa-SUBUNIT GENE
AND THE LONG-TERM PROGNOSIS FOR PATIENTS WITH HEART FAILURE
E-mail: sn_p@ukr.net
Forecasting of an unfavorable course in heart failure is very relevant. The purpose of the work was to determine the effect of the G protein P3-subunit C825T (RS5443) gene polymorphism on the long-term prognosis for patients with heart failure. The study included 170 patients with heart failure on the background of post-infarction cardiosclerosis. The G protein P3-subunit C825T (RS5443) gene polymorphism was determined by means of the polymerase chain reaction. Daily monitoring of ECG, Doppler echocardioscopy were carried out. The observation period was 3 years, whereby the course of the disease was evaluated, the atrial fibrillation paroxysms development, the frequency of hospitalizations due to the disease decompensation, and mortality were taken into account. The frequencies of the C825T (RS5443) polymorphic variants of the G protein P3-subunit gene were determined in the patients. 47% of patients are homozygous carriers of C825 alleles, 47% of patients are heterozygotes (C825T), 11 out of 170 patients are homozygous by the T genome. Homozygous patients with T genome are younger by 7.5 years, compared to homozygous C-allele patients and by 6 years younger compared to heterozygotes (CT) (p <0.01). For 3 years, in the patients homozygous by the T-allele, an increase in the left ventricle end-diastolic volume (by 6%, p <0.05) and a decrease in the amount of left ventricular ejection fraction (by 11%, p <0.05) was observed. In 5 out of 11 patients with heart failure who are homozygous by the T allele (TT), in the third year of observation, a pathological number of ventricular extrasystoles is recorded. Among the homozygous by the C-allele (CC) and heterozygous (CT) patients, this type of rhythm disorder is statistically reliably less frequent (x2 = 6.854; p <0.05). The tendency was revealed towards a higher frequency of hospitalization in patients due to the disease decompensation for 3 years in the group of homozygous patients with T-allele.
Key words: heart failure, clinical course, atrial fibrillation, C825T (RS5443) polymorphism, gene, P3 subunit of
G protein.
The study is a fragment of the research project "Development of methods for preventing the unfavorable course of chronic heart failure with account of the pharmacological and genetic profile of patients and concomitant pathology", state registration No. 0116U003038.
The result of heart diseases is heart failure (HF). This pathology is an actual medical and social problem in our country [2]. The prevalence of HF among the adult population ranges from 1.5 to 5.5% and grows pro rata with age [1]. The fact that about half of the patients die within 4 years is also a sign of the HF prognosis severity [2]. Prediction of an unfavorable HF flow is important for a number of reasons. One of them is selection of patients requiring more intensive observation and treatment [5, 6].
The P-adrenergic receptors (P-AR) are paired transmembrane proteins, which are found in cells throughout the body, including cardiomyocytes and blood vessels smooth myocytes. There are three subclasses of AR (P1, P2, P3). P1- and P2-AR affect the of the cardiovascular system's (CVS) physiology. P-AR stimulates catecholamines on intracellular processes through the cytosolic G protein, i.e. heterotrimer consisting of three subunits: a, P, and g. G-proteins are expressed in all human cells. The most frequent C825T polymorphism of the P3-subunit gene (GNB3) is associated with an increase in the activity of signaling pathways. In the CVS, this polymorphism primarily affects vascular reactivity and cardiomyocytes growth [14].
However, whether the indicated genomic variation affects the HF course, according to previous studies, remains unclear [14]. T-allele has a high prevalence among the black race representatives, compared to europoids [9]. Approximately 50% of Africans are homozygotes by the GNB3 TT genotype. Meanwhile, only 10% of Europeans are alike. In the genetic study "African-American Heart Failure Trial" (AHeFT), homozygote by T allele (GNB3 TT) patients had the most adverse pathogeny in the placebo group and received the most benefit from therapy [9]. Despite the clear racial differences in the mutations frequency, there are only stand-alone and quite contradictory results of studies on the GNB3 TT genotype impact on the HF progression in Europeans. This inspires to new studies in this field.
The purpose of the study was to determine the G-protein P3-subunit's C825T (RS5443) gene polymorphism influence on the long-term prognosis for patients with HF.
Material and methods. The study included 170 patients with HF (100 women and 70 men) of the European race. The involvement criteria were: signing the Patient Informed Consent, the left ventricle (LV) systolic dysfunction on the background of post-infarction cardiosclerosis. HF diagnosis and treatment of patients were carried out in accordance with the recommendations of the European Society of Cardiologists and the Ukrainian Association of Cardiologists [10, 3]. The observation period lasted 3 years, whereby the
© S.M. Pyvovar, Yu.S. Rudyk, 2019
HF course was evaluated, with account of the atrial fibrillation paroxysms development, the frequency of hospitalizations for the disease decompensation and mortality.
Doppler echocardioscopy was performed using the VIVID-3 ultrasonic diagnostic system, (General Electric, USA). The calculations of the left ventricle end-diastolic volume (LVEDV) values, left ventricle end-systolic volume (LVESV), left ventricle ejection fraction (LVEF) were performed. The diameter of the left atrium (LA), the right ventricle (RV) and other parameters were determined [4].
Types of cardiac rhythm and conduction disorders and their daily number were studied by daily ECG monitoring using the CardioSens computerized system for ECG monitoring (CDS, Ukraine). The pathology of the Extra Systoles Ventriculaire (ESV) daily number was evaluated according to the criteria given in the European Society of Cardiology recommendations (2015) [11].
Molecular genetic study of the G protein p3- subunit C825T (RS5443) gene (GNB3) polymorphism was performed by means of the polymerase chain reaction (PCR). The material for the genetic study was leukocytes of the patients' peripheral blood. Peripheral blood was obtained by blood sampling from the cubital vein in fasting state in the amount of 4 ml in a vacuum collection tube with EDTA (8.4 mg K3-EDTA). The genomic DNA isolation from blood leukocytes for molecular genetic studies was carried out using the "DNA-sorb-B" commercial kit (AmpliSens, Russia) in accordance with the instructions for the kit. Samples were stored at minus 20oC prior to the amplification.
Amplification of the isolated DNA was carried out automatically in the TP4-PCR-01 - "Tercyk" thermocycler using the "GenePak PCR Core" commercial reagents kit ("IzoGen" Laboratory, Russia) and specific primers ("Thermo Scientific", Lithuania). To the final PCR mixture, "GenePak PCR Core", 50 ng of genomic DNA and 20 pmoles of each specific primers pair were introduced (the total volume of the mixture was 20 ^l). The primer sequences specified in the paper were applied [14].
Testing the equality of means hypothesis in the two groups was carried out using the two-sample t-test. When comparing data in the monitoring dynamics, the one-sample t-test was used. When analyzing data in more than two patients' groups simultaneously, one-factor dispersion analysis (ANOVA - Analysis of variance, deviation analysis) was used. Assessment of the difference in the signs frequencies in the groups was carried out according to Pearson's yl criterion (with the Yates correction for the signs number less than 10). The data are presented in the formula M ± SD, where M is the mean value, SD is the standard deviation. The calculations were performed using the SPSS statistical package for Windows.
Results of the study and their discussion. While analyzing the data, it was found that among 170 patients with HF, 80 (47%) were homozygous carriers of the C825 (CC) allele. The total of 11 out of 170 patients had two T825 (TT) alleles. The total of 79 (475%) patients with HF were heterozygotes (CT).
Clinical profiles of the patient groups, depending on the specified gene polymorphism, are demonstrated in table 1.
Table 1
Clinical profiles of patients with different G protein gene 03-subunit C825T (RS5443) polymorphisms
at baseline
Parameter C825T (RS5443) polymorphism P
CC (n = 80) CT (n = 79) TT (n = 11)
Age, years 66.8 ± 10.8 65.3 ± 9.8 59.3 ± 7.8 * < 0.01
FC NYHA (% I/II/III/IV) 10.0/40.0/35.0/15.0 12.7/34.2/35.5/17.6 9.1/36.5/36.4/18 > 0.05
HR, min.-1 65.3 ± 17.5 68.7 ± 15.9 67.6 ± 11.3 > 0.05
SAP, mm Hg 128.4 ± 26.3 120.2 ± 25.3 122.5 ± 27.1 > 0.05
DAP, mm Hg 74.1± 11.9 72.9± 11.5 75.5 ± 13.1 > 0.05
ACE inhibitors 68 (85.0 %) 71 (89.9 %) 10 (90.9 %) > 0.05
Aldosterone receptor antagonists 32 (40.0 %) 30 (38.0 %) 4 (36.4 %) > 0.05
ß-adrenergic blockers 72 (90 %) 73 (92.4 %) 10 (90.9 %) > 0.05
Note: * - probability of difference in homozygous patients by T-allele, compared to homozygous patients by C-allele and heterozygotes.
At baseline, the group of patients probably did not differ against each other according to the HF functional classes (NYHA), heart rate (HR), systolic (SAP) and diastolic arterial pressure (DAP), angiotensin converting enzyme inhibitors, P-blockers and spironolactone. Meanwhile, at baseline, homozygous patients with T-alleles were younger by 7.5 years compared to homozygous patients with C allele and by 6 years compared to heterozygotes. The difference was significant (p <0.01).
At baseline, patients with a different G-protein P3-subunit C825T (RS5443) gene polymorphism did not differ in the main parameters of the intracardiac hemodynamics (table 2).
Table 2
Parameters of intracardiac hemodynamics in patients with different G protein gene 03-subunit C825T
(RS5443) polymorphism
Parameter C825T (RS5443) polymorphism P
CC (n = 80) CT (n = 79) TT (n = 11)
1 2 3
Baseline period
EDV, ml 190.4 ± 42.5 201.2 ± 45.8 193.9 ± 36.2 > 0.05
ESV, ml 118.8 ± 31.7 123.8 ± 33.1 118.2 ± 28.8 > 0.05
LVEF, % 37.6 ± 8.8 38.5 ± 8.6 39.04 ± 5.9 > 0.05
LA, cm 4.3 ± 1.5 4.5 ± 1.5 4.4 ± 1.2 > 0.05
RV, cm 3.2 ± 1.1 3.1 ± 1.0 3.4 ± 0.9 > 0.05
3 years after the baseline
EDV, ml 193.2 ± 38.2 198.5 ± 40.2 205.9 ± 15.1*(3-1 Ta 3-2) < 0.05
ESV, ml 120.0 ± 32.1 119.3 ± 32.9 134.4 ± 21.5 > 0.05
LVEF, % 37.9 ± 9.2 39.9 ± 7.0 34.7 ± 4.6§; *(3-1 Ta 3-2) < 0.05
LA, cm 4.4 ± 1.6 4.3 ± 1.7 4.5 ± 1.0 > 0.05
RV, cm 3.2 ± 1.5 3.2 ± 1.3 3.5 ± 1.1 > 0.05
Note: *(3-1 and 3-2) - probability of difference between groups 3 and 1, groups 3 and 2; § - probability of difference in the monitoring
dynamics.
While analyzing the parameters of intracardiac hemodynamics, obtained in the 3rd year of observation, it was found that in the homozygous patients with T allele, an increase in left ventricular EDV was observed, compared to the baseline (by 6%, p <0.05), and a decrease in the left- ventricle ejection fraction (LVEF) value (11%, p <0.05) (see table 2). Similar probability patterns were not found in the group of homozygous by C allele (CC) and heterozygous (CT) patients.
In the third year of observation, LVEDV in the group of homozygous patients with T-allele (TT) were significantly higher compared to that in patients homozygous by C allele (CC) and heterozygotes (CT) (7% and 4% respectively, at p < 0.05). The left ventricular ejection fraction in patients with TT genotype was 8% lower compared to that in homozygous patients with C allele (SS) and 9% compared to those with CT genotype (p <0.05).
Analysis of the rhythm disorders development frequency within 3 years was carried out. The observation showed no reliable difference in the rate of atrial fibrillation (AF) development in patients with HF with a different G protein gene P3-subunit C825T (RS5443) polymorphism (table 3).
Table 3
Frequency of rhythm disorders development in patients with HF during 3 years of observation (n = 170)
Rhythm disorder C825T (rs5443) polymorphism
CC (n = 80) CT (n = 79) TT (n = 11)
AF (n = 49) 22 (28 %) 25 (32 %) 2
AF not found (n = 121) 58 (73 %) 54 (68 %) 9
X2 = 0.982; p > 0.05
ESV (n = 29) 13 11 5
ESV not found (n = 141) 67 (84 %) 68 (86 %) 6
X2 = 6.854; p < 0.05
Herewith, in the group of patients who are homozygous by the T-allele in the third year of observation, 5 of 11 patients are registered with ESV in a pathological amount. Meanwhile, in the groups of patients homozygous by the C-allele and heterozygous (CT), this type of rhythm disorder was detected in 16% and 14%, respectively (table 3). The difference is statistically reliable (x2 = 6.854; p <0.05).
Further analysis has shown that the highest incidence of hospitalization for 3 years due to the pathology decompensation was observed in patients with HF, which were homozygotes for the T-allele (in 6 of 11 patients) (table 4), comparing to that among homozygous and heterozygous patients for the C-allele (26% and 22%, respectively). But the difference does not reach the statistically significant level (x2 = 5,501; p = 0,064) and becomes biased.
There was no reliable correlation between the 3-year mortality with the polymorphism of this gene among patients with HF (see table 4). Three-year mortality among homozygous T-alleles in patients with HF was 18% (2 out of 11 patients), in patients homozygous by the C-allele - 19%, among heterozygotes -17% (x2 = 0.146; p> 0.05).
Table 4
HF course during 3 years of observation (n = 170)
HF course C825T (RS5443) polymorphism
CC (n = 80) CT (n = 79) TT (n = 11)
Hospitalization due to HF decompensation (n = 44) 21 (26 %) 17 6
Hospitalization not registered (n = 126) 59 (74 %) 62 (79 %) 5
X2 = 5.501; p = 0.064
Unfavourable course (mortality) (n = 30) 15 13 2
Favourable course (n = 140) 65 (81 %) 66 (84 %) 9
X2 = 0.146; p > 0.05
Although genetic predisposition is increasingly considered as a risk factor for cardiovascular diseases, the role of the genomic factor in the development and progression of HF remains largely unexplored. In our study, it has been demonstrated that in patients homozygous by the T-allele of the C825T (RS5443) polymorphism of the G protein gene p3-subunit, an increase in LVEDV (by 6%, p <0.05) and a reduction of LV ESV value (11 %, p <0.05) have been observed for 3 years. Similar regularities were not found in the group of homozygous by the C-allele (CC) and heterozygote (CT) patients.
In spite of the fact that T-polymorphism is functionally inactive, it leads to truncated (alternative) splicing of exon 9 (GNB3) and ultimately to the "truncated" P3 subunit of G-protein. This "truncated" subunit increases a-adrenergic activation. Frequently, this mutation is the cause for an early manifestation (from 17 years of age) of the low-renin variant of arterial hypertension in African Americans [13]. We have not established the dependence of the AP level on this polymorphism, although the correlation could be distorted by using both the ACE inhibitors and P-blockers in most of these patients.
The influence of GNB3 polymorphism on the HF course was studied in the AHeFT genetic study involving African Americans [8]. In the trail, patients with the GNT3 TT genotype in the placebo group had a high mortality rate compared to the C-allele carriers. Also, homozygotes by the T-allele were in the most fortunate position due to the combination of isosorbide dinitrate and hydralazine in a fixed combination. These data may indicate that the GNB3 genotype affects the pharmacotherapy efficacy in African Americans with HF. We note that although nearly all the patients in our study were treated with P-blockers and ACE inhibitors, we did not prescribe the combination of isosorbide dinitrate with hydralazine. Could the use this combination to improve the course of HF in Europeans in the presence of GNT3 TT genotype, remains uncertain.
The genotypes' effect on cardiac remodeling and LVEF in patients with HF was studied in AHeFT and in small trails. The studied genotypes referred to the genes encoding renin-angiotensin aldosterone systems [8], nitric oxide synthesis [8] and adrenoreceptors. These genes have been studied as potentially affecting myocardial remodeling and the therapy efficacy. On the contrary, the AHeFT study did not obtain data on the effects of the GNB3 TT genotype on myocardial remodeling in patients with HF [9]. In addition to the data obtained in the AHeFT study, another report has demonstrated that the GNB3 T-allele may be associated with an increase in arrhythmic events in patients with HF [7]. In Schmitz B, et al (2014) [12], the GNB3 gene mutation was associated with an reverse remodeling after resynchronizing device implantation in patients with HF [12].
The data obtained by us, on the fact that in 5 out of 11 patients with HF, homozygous by the Tallele (TT), in the third year of observation, ESV is recorded in a pathological amount, comparing to the frequency of this rhythm disorder development among homozygous by the C-allele (CC) and heterozygous (CT) patients (x2 = 6.854; p <0.05), probably agree with the results of a study performed by Chemello D. at al. (2010) [7]. The authors have demonstrated that the G protein gene p3-subunit T825 polymorphism is associated with a higher rate of discharge in patients with HF having a defibrillator cardioverter implanted for ventricular tachycardia.
1. Frequency of G-protein b3-subunit C825T (RS5443) gene polymorphous variants among patients with HA was determined. The amount of 47% patients are homozygous carriers of C825 allele, 47% of patients are heterozygotes (C825T), 11 of 170 patients are homozygotes by the T-allele.
2. Homozygous patients by the T-allele are younger by 7.5 years compared to homozygous patients by the C allele and by 6 years younger compared to heterozygotes (p <0.01).
3. For 3 years, in HF patients with homozygous T-allele, a growth in the diastolic volume of the left ventricle (LVEDV) (by 6%, p <0.05) and a decrease in the size of the left ventricular ejection fraction
(LVEF) (by 11%, p <0, 05) were observed. Similar regularities were not found in the group of homozygous by the C allele (CC) and heterozygous (CT) patients.
4. In 5 out of 11 HF patients, homozygous by the T-allele (TT), in the third year of observation, ESV is registered in a pathological amount. Among the homozygous by the C-allele (CC) and heterozygous (CT) patients, this type of rhythm disorder is reported to be reliably less frequent (%2 = 6.854; p <0.05).
5. The tendency towards a higher rate of hospitalization has been revealed for patients with HF decompensation for the 3 years period in the group of patients homozygous by the T allele (6 out of 11 patients), comparing to that among homozygous and heterozygous patients with C-allele (26 and 22%, respectively) (x2 = 5.501; p = 0.064).
6. Our study is confined to a small number of patients, which reduces the strength of data on the genetic association between the GNB3T allele and left ventricular myocardial remodeling in HF patients with post-infarction cardiosclerosis. But the probable patterns of GNB3 TT influence on the HF course can demonstrate the strong influence of this mutation and indicate that this allele is not only a race marker. The results are likely to require further research involving a large cohort of patients.
1. Voronkov LH, Dzyak GV, Amosova YeN, Bagriy AE, Volkov VI, Lutay MI. Obosnovaniye, dizayn i rezultaty ukrainskogo mnogotsentrovogo issledovaniya KORIOLAN (KORIOL - Alternativa nasosnoy nedostatochnosti serdtsa). Sertseva nedostatnist. 2015; 2:28-33. [in Russianl
2. Voronkov LH, Ilnytska MR, Babych PM. Prohnoz patsiyentiv iz khronichnoyu sertsevoyu nedostatnistyu ta systolichnoyu dysfunktsiyeyu livoho shlunochka zalezhno vid danykh neinvazyvnykh metodiv obstezhennya. Ukr ter zhurn. 2015;1:24-31. [in Ukrainian]
3. Voronkov LH. ed. Rekomendatsiyi Ukrayinskoyi asotsiatsiyi kardiolohiv z diahnostyky, likuvannya ta profilaktyky sertsevoyi nedostatnosti u doroslykh. Robocha hrupa Ukrayinskoho naukovoho tovarystva kardiolohiv. Kyiv: Chetverta khvylya; 2012. 47 p. [in Ukrainian]
4. Lang RM, Bierig M, Devereux RB, Flachskampf FA, Foster E, Pellikka PA, et al. Rekomendatsii po kolichestvennoy otsenke struktury i funktsii kamer serdtsa. Rossiyskiy kardiologicheskiy zhurnal. 2012; 3(95) prilozheniye:1-28 [in Russian]
5. Pyvovar S. Zalezhnist perebihu sertsevoyi nedostatnosti vid polimorfizmu Gln27Glu hena b2-adrenoretseptoriv. Ukr ter zhurn. 2016.; 3: 50-5 [in Ukrainian]
6. Rudyk Yr. Khronicheskaya serdechnaya nedostatochnost i geneticheskiy polimorfizm: rol b-adrenoretseptorov. Sertseva nedostatnist. 2009; 2: 20-2 [in Russian]
7. Chemello D, Rohde LE, Santos KG, Silvello D, Goldraich L, Pimentel M, et al. Genetic polymorphisms of the adrenergic system and implantable cardioverter-defibrillator therapies in patients with heart failure. Europace. 2010; 12:686-691.
8. McNamara DM, Tam SW, Sabolinski ML, Tobelmann P, Janosko K, Venkitachalam L, et al. Endothelial nitric oxide synthase (NOS3) polymorphisms in African Americans with heart failure: results from the A-HeFT trial. J Card Fail. 2009; 15:191-198.
9. McNamara DM, Taylor AL, Tam SW, Worcel M, Yancy CW, Hanley Yanez K, et al. G-protein beta-3 subunit genotype predicts enhanced benefit of fixed-dose isosorbide dinitrate and hydralazine: results of A-HeFT. JACC Heart Fail. 2014; 2:551-557.
10. Ponikowski P, Voors A, Anker D, John GF, Andrew JS, Falk C, et al. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2016. The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. European Heart Journal. 2016 June 8: 123.
11. Priori SG, m-Lundqvist CB, Mazzanti A, Blom N, Borggrefe M, et al. 2015 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death. The Task Force for the Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death of the European Society of Cardiology (ESC). European Heart Journal. 2015; 36: 2793-2867.
12. Schmitz B, De Maria R, Gatsios D, Chrysanthakopoulou T, Landolina M, Gasparini M, et al. Identification of genetic markers for treatment success in heart failure patients: insight from cardiac resynchronization therapy. Circ Cardiovasc Genet. 2014; 7: 760-770.
13. Schunkert H, Hense HW, D^ing A, Riegger GA, Siffert W. Association between a polymorphism in the G protein beta3 subunit gene and lower renin and elevated diastolic blood pressure levels. Hypertension. 1998;32:510-513.
14. Sheppard R, Hsich E, Damp J, Elkayam U, Kealey A, Ramani G, et al. Investigators GNB3 C825T Polymorphism and Myocardial Recovery in Peripartum Cardiomyopathy Results of the Multicenter Investigations of Pregnancy-Associated Cardiomyopathy Study. Circ Heart Fail. 2016; 9: e002683.
ПОЛ1МОРФ1ЗМ С825Т (Я85443) ГЕНА 0з-СУБОДИНИЦ1 С-ПРОТЕ1НУ ТА В1ДДАЛЕНИЙ ПРОГНОЗ ХВОРИХ З СЕРЦЕВОЮ НЕДОСТАТШСТЮ Пивовар С.М., Рудик Ю.С., Лозик Т.В., Гальчшська В.Ю.
Прогнозування несприятливого плину серцево! недостатносп е вельми актуальним. Метою роботи було визначення впливу полiморфiзму С825Т (Б55443) гена вз-субодинищ О-проте!ну на владений прогноз хворих з серцевою недостатшстю. До дослщження включено 170 хворих з серцевою недостатшстю на фош тсля шфарктного кардюсклерозу. За допомогою полiмеразноí ланцюгово! реакцп визначали полiморфiзм С825Т
ПОЛИМОРФИЗМ С825Т (Я85443) ГЕНА Рз-СУБЪЕДИНИЦЫ С-ПРОТЕИНА И ОТДАЛЕННЫЙ ПРОГНОЗ БОЛЬНЫХ С СЕРДЕЧНОЙ
НЕДОСТАТОЧНОСТЬЮ Пивовар С.Н., Рудык Ю.С., Лозик Т.В., Гальчинськая В.Ю.
Прогнозирование неблагоприятного течения сердечной недостаточности является весьма актуальным. Целью работы было определение влияния полиморфизма С825Т (Б55443) гена вз-субъединицы О-протеина на отдаленный прогноз больных с сердечной недостаточностью. В исследование включено 170 больных с сердечной недостаточностью на фоне послеинфарктного кардиосклероза. С помощью полимеразной цепной реакции определяли полиморфизм
(¿85443) гена Рз-субодинищ О-проте'ша. Проводили добове мошторування ЕКГ, Допплер-ехокардiоскопiю. Перiод спостереження склав 3 роки, протягом якого оцшювали перебiг захворювання, враховували розвиток пароксизмiв фiбриляцi'l передсердь, частоту госпiталiзацiй з приводу декомпенсацй захворювання, смертшсть. Визначено частоту полiморфних варiантiв С825Т (¿85443) гена Рз-субодиницi О-проте'шу серед хворих. 47 % пащенив е гомозиготними носiями алелi С825, 47 % пацieнтiв - гетерозиготи (С825Т), 11 з 170 хворих е гомозиготами за Т алелем. Гомозиготш хворi за Т алелем молодшi на 7,5 роюв, порiвняно до гомозиготних пащенив за С алелем та на 6 роюв порiвняно з гетерозиготами (р < 0,01). На протязi 3 рокiв у гомозиготних за Т алелем хворих спостертаеться збшьшення кiнцево-дiастолiчного об'ему лiвого шлуночка (на 6 %, р < 0,05) та зменшення величини фракцй викиду лiвого шлуночка (на 11 %, р < 0,05). У 5 з 11 хворих з серцевою недостатшстю, що е гомозиготними за Т алелем (ТТ) на третш рж спостереження у рееструеться патологiчна юльюсть шлуночково! екстрасистолй. Серед гомозиготних за С алелем (СС) та гетерозиготних (СТ) пацiентiв даний вид порушення ритму рееструеться вiрогiдно рiдше (х2 = 6,854; р < 0,05). Виявлено тенденщю до бшьшо! частоти госпiталiзацii хворих з приводу декомпенсацй серцевоi' недостатност протягом 3 роюв в груш пащен™, що е гомозиготами за алелем Т.
Ключовi слова: серцева недостатшсть, клiнiчний перебiг, фiбриляцiя передсердь, С825Т (¿85443) полiморфiзм, ген, Р3-субодиниця О-протеша.
Стаття надiйшла 10.09.18 р.
С825Т (¿85443) гена в3-субъединицы О-протеина. Проводили суточное мониторирование ЭКГ, Допплер-эхокардиоскопию. Период наблюдения составил 3 года, в течение которого оценивали течение заболевания, учитывали развитие пароксизмов фибрилляции предсердий, частоту госпитализаций в связи с декомпенсацией заболевания, смертность. Определены частоты полиморфных вариантов С825Т (¿85443) гена в3-субъединицы О-протеина среди больных. 47% пациентов - гомозиготные носители аллели С825, 47% пациентов - гетерозиготы (С825Т), 11 из 170 больных является гомозиготами по Т геному. Гомозиготные больные с Т геном моложе на 7,5 лет, по сравнению с гомозиготных пациентов по С алели и на 6 лет по сравнению с гетерозиготами (СТ) (р <0,01). На протяжении 3 лет в гомозиготных по Т алели больных наблюдается увеличение конечного диастолического объема левого желудочка (на 6%, р <0,05) и уменьшение величины фракции выброса левого желудочка (на 11%, р <0,05). В 5 из 11 больных с сердечной недостаточностью, которые является гомозиготными по Т аллели (ТТ) на третий год наблюдения регистрируется патологическое количество желудочковой экстрасистолии. Среди гомозиготных по С аллели (СС) и гетерозиготных (СТ) пациентов данный вид нарушения ритма регистрируется достоверно реже (х2 = 6,854; р <0,05). Выявления тенденции к большей частоте госпитализации больных в связи с декомпенсации заболевания на протяжении 3 лет в группе гомозиготных больных по Т аллели.
Ключевые слова: сердечная недостаточность, клиническое течение, фибрилляция предсердий, С825Т (¿85443) полиморфизм, ген, в3-субъединица О-протеина.
Рецензент Катеренчук 1.Г.
DOI 10.26724/2079-8334-2019-1-67-93 УДК 340.1:614.2
ЗДОРОВ'Я ЯК ПРАВОВА КАТЕГОР1Я
E-mail: alya.kozhushko@gmail.com
У стата розкриваеться змют термшу «здоров'я» з правово! точки зору. Аналiзуються pi3Hi тдходи до висв^лення поняття здоров'я фiзично'l особи як немайнового блага. Окрема увага придтена з'ясуванню змюту поняття «здоров'я» вiдповiдно до вщкрнто! концепци здоров'я. Окрiм того, у стата наводиться критика чинного легального визначення здоров'я з точки зору його використання у правовш сфер^ Обгрунтовано необхщшсть включення у змют поняття здоров'я не лише соматично!, а й пс^чно! складово!. Зроблено висновок, що здоров'я як особисте немайнове благо повинно охоплюватись наявним соматичним та психiчним станом життeдiяльностi оргашзму, який визначаеться системою яюсних та кiлькiсних медичних показникiв.
Ключовi слова: здоров'я, психiчне здоров'я, соматичне здоров'я, немайнове благо, право на здоров'я, правозастосування.
Вщповщно до статт 3 Конституци Украши життя та здоров'я людини е вищою сощальною цшнютю. Таке високе визнання цього фундаментального особистого немайнового блага людини обумовлюе його глибоку штегращю до правово! матери, створюючи людиш низку правових можливостей, яю спрямоваш на використання та охорону вказаного блага.
Правова регламентащя можливостей у сфер! власного здоров'я ф1зично! особи на сьогодш визначаеться закршленням низки прав, що пов'язаш 1з здоров'ям, зокрема, право на усунення небезпеки, яка загрожуе здоров'ю (ст. 282 ЦК Украши), право на охорону здоров'я (ст. 283 ЦК Украши), право на медичну допомогу (ст. 284 ЦК Украши), право на шформащю про стан свого здоров'я (ст. 285 ЦК Украши), право на таемницю про стан здоров'я (ст. 286 ЦК Украши) тощо. Переважно така правова регламентащя е фактичним калькуванням вщповщних положень Конституцн Украши (ст. 49), або положень шшого законодавства.
© Р.О. Стефанчук, А.О. Янчук, 2019
