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DOI 10.14526/02_2018_332
INTERCONNECTION OF ACE AND NOS3 GENES POLYMORPHISM WITH THE LEVL OF ARTERIAL PRESSURE AMONG ATHLETES OF THE SAKHA (YAKUTIA)
REPUBLIC
Mestnikova E.N.1, Makharova N. V.1, Zakharova F.A.2, Akhmetov I.I.3, Pinigina I.A.1
1Center for Sports Medicine and Rehabilitation of the Sakha Republic (Yakutia) Higher Sports
Skills School, Russia, Yakutsk, katemestnikova@mail.ru 2Medical Institute North-Eastern Federal University named after. M.K. Ammosov
Russia, Yakutsk Kazan State Medical University Russia, Kazan
Annotation. The article presents the results of arterial pressure (AP) level study and polymorphism of genes of angiotensin-converting enzyme (ACE) and endothelial nitric oxide synthase (eNOS) analysis among sportsmen, who go in for different kinds of sports. Materials. 135 Yakut sportsmen (men, 22,3±4,2 years old; masters of sport and candidate masters of sport), who specialize in combat sports and cyclic kinds of sport. Research materials: scientific literature analysis and summarizing, monitoring, methods of mathematical statistics. Results. Prevalence rate of arterial hypertension (AH) analysis according to the results of daily monitoring of arterial pressure (DMAP) showed that 56 (41,5%) sportsmen had a high level of AP, 79 (58,5%) sportsmen had normal AP level. At the same time, no statistically valid dependence of AH on a kind of sport was revealed (x2=3,48, df=1, p=0,062). Among people with a high AP level the carriership of allele D gene of ACE was 67,8% contrary to 48,1% of people with a normal AP level. Homozygous genotype ACE DD carriership was revealed among 25% of sportsmen with a high AP level and 11,4% of people with normal AP level. Statistical analysis showed that the chance of allele D carriership among examined sportsmen with AH is twice higher, than allele I carriership (95% Di Osh 1,1 - 3,7). Relative chance to have homozygous genotype DD is 2,5 times higher (95% Di Osh 1,03 - 6,5), than among the carriers of other genotypes. eNOS genotypes distribution deviates from Hardy-Weinberg balance. Conclusion. The received results correspond with the results of other research works concerning polymorphism of ACE gene influence on AP level among young people. Keywords: angiotensin-converting, sportsmen, physical loads.
For citations: Mestnikova E.N., Makharova N.V., Zkharova F.A., Akhmetov I.I., Pinigina I.A. Interconnection of ACE and eNOS genes polymorphism with the level of arterial pressure among athletes of the Sakha (Yakutia) Republic. The Russian Journal of Physical Education and Sport (Pedagogico-Phycological and Medico-Biological Problems of Physical Culture and Sports). 2018; 13(2): 194-199. DOI 10.14526/02_2018_332
URGENCY
Arterial pressure (AP) among sportsmen is one of the most important indices of adaptation level and functional state of cardiovascular system. Normal fluctuations range for systolic pressure among sportsmen is 100-129 millimeters of mercury, for diastolic pressure - 60-79 millimeters of
mercury [2]. There are research works, according to which, depending on the type of blood circulation and power of fulfilled physical loads, difficult adaptive changes happen in cardiovascular system. These changes are seen in the diversity of different variants to physical load reaction [1].
It is known, that arterial hypertension (AH) is one of the most often revealed cardiovascular system pathology among sportsmen. Etiology and pathogenesis of arterial hypertension development among sportsmen have much in common with etiology and pathogenesis in general population: owing to genetic predisposition, way of life, metabolic disorder, atherosclerosis and others. As it is known, physical over-tension provides many systems of an organism mobilization and it makes professional sports lessons an independent risk factor of AH development among young people [9]. In the work by Ronzhina O.A. (2014) it was revealed that more than half of the examined sportsmen, who train power quality, had isolated systolic arterial hypertension. At the same time, among 25% of the respondents hypertension was revealed only with the help of daily monitoring of arterial pressure (DMAP). Thus, the author comes to the conclusion, that professional sport, especially with static loads of high intensity, can be accompanied by the risk of AH formation [6].
One more important, independent factor, which causes AH formation among sportsmen, is psycho-emotional stress. "Popularity load", precompetitive stress, which lead to sympathoadrenal system activation, adrenalin, noradrenaline, cortisol excretion increases cause heart rate and AP increase [7].
However, in spite of equal sports experience and level of loads, not all sportsmen have arterial hypertension. It gives the reason to consider genetic factor impact in AH formation among young people.
Nowadays genes study, associated with cardiovascular diseases, is a very urgent direction. B. Rigat, L. Tiret and others, having examined the group of healthy people, set, that gene polymorphism of angiotensin-converting enzyme (ACE) conditions plasma level of ACE, moreover, a higher level of this enzyme is revealed among homozygotes of D allele (DD) [12, 13]. Danser and other authors
also revealed, that DD homozygotes have higher ACE concentration in plasma and level of tissular ACE, than people with ID and II genotype [7]. Thus, the held research works show that polymorphism of ACE gene can determine the level of II angiotensin and DD genotype of ACE gene is considered the predictor of myocardial hypertrophy among people with hypertensive disease and hypertrophic cardiomyopathy [4, 10]. In 1994 H. Schunkert and other authors examined young people with a normal AP level and revealed interconnection between DD genotype and left ventricular hypertrophy according to electrcardiographic criteria [12]. Later in other research works with the help of echocardiography association of DD genotype with a high volume of left ventricular mass was proved [10].
One of the most studied genes, associated with cardiovascular diseases, is also gene of endothelial nitric oxide synthase (eNOS). Polymorphism of eNOS gene Glu298Asp (G894T) and -786T>C were analyzed in several meta-studies. J.P. Casas, B. Wolff with other authors studied polymorphism of eNOS gene in case of ischemic heart disease and revealed considerable differences in frequency of T and C alleles in ethnic groups [8, 15]. In the research work of T.V. Kosyankova (2012) and other authors, where ethnic diversity of population of Siberia was taken into account, it was stated that polymorphism of G894T gene eNOS is the risk factor of coronary atherosclerosis and essential arterial hypertension development [5].
The aim of the research work is to determine interconnection between polymorphism of ACE and eNOS genes and the level of arterial pressure among sportsmen of Yakut population.
MATERIALS AND METHODS
In order to achieve the set aim 135 Yakut male athletes at the age of 18-30 (the average age - 22,3±4,2 years-old) were examined. All examined people are sportsmen of high sportsmanship: masters of sport and candidate masters. Among 135 respondents there were
109 sportsmen- combatants (free-style wrestling, surdowrestling, boxing, kickboxing, taekwondo, mixed martial arts) and 26 sportsmen, who go in for cyclic kinds of sport (marathon, semi-marathon, racewalking, biathlon, cross-country skiing, average distances running). In order to estimate the level of AP all respondents went through daily monitoring of arterial pressure (DMAP) using portable arterial pressure recorder MDP-NS-02s "DMS Progressive technologies" (Russia). AP estimation was realized with the help of oscillometric method in the phase of decompression. Multiplicity of AP measurements during the day was each 20 minutes, at night - each 30 minutes, according to World Health Organization recommendations. In order to avoid the errors of automated measurement of AP triple control measurement of AP using Korotkov method was held at the beginning and in the end of DMAP with further correction of measurement results. All respondents had a diary, where they recorded their actions during the research (physical activity, sleep, eating, taking medicaments). The data analysis was held in case of successful measurements more than 70% of the whole measurements during a day. AH criteria corresponded with the average daily systolic arterial pressure (SAP) and diastolic arterial pressure (DAP) more than 130 and 80 millimeters of mercury, with the average daytime SAP and DAP - more than 135 and 85 millimeters of mercury, the average night SAP and DAP- more than 120 and 70 millimeters of mercury [3]. With the help of polymerase chain reaction (PCR) method with further restriction of amplification product - RAD analysis among all respondents' polymorphism of gene was determined (ACE, polymorphism Alu I/D (rs4646994)), endothelial nitric oxide synthase (eNOS) gene (NOS3, polymorphism Glu298Asp (G/T) (rs1799983)). Statistical handling of the received results was realized with the help of STASTISTICS
program (SPSS version 19, IBM Company, the USA) and OpenEpi (Version 3.01). Correspondence estimation of ACE gene genotypes frequency with Hardy-Weinberg balance was calculated according to the following formula:
Exp(AA)=p2n Exp(AB)=2pqn Exp(BB)=q2n, where Exp (AA, AB, BB) is expected (absolute) frequency of AA, AB, BB genotype, p - A allele frequency, q- B allele frequency, n- general number of the respondents.
Real distribution of genotypes comparison with the expected distribution was realized using chi-square criteria. Groups comparison according to qualitative features was held with the help of fourfold contingency table using Pearson chi-square. Chances ratio was calculated using x2 criterion with 95% confidence interval in OpenEpi (Version 3.01) software program. Critical importance level (p) was 5%.
RESEARCH RESULTS AND THEIR DISCUSSION
Prevalence of arterial hypertension analysis according to the results of DMAP revealed that 56 sportsmen had arterial hypertension, which is 41,5% of general number of the examined sportsmen. Normal AP level was among 79 (58,5%) sportsmen (picture 1). The received percentage of high frequency of AH among sportsmen corresponds with the results of other scientists. V.S.Bubunova studied 100 young men (average age-23,6) and revealed an isolated systolic AH among one third of people with normal level of AP. In the work of O.A. Ronzhina 80 sportsmen, who train power (average age- 21,5), were examined. Arterial hypertension was revealed among 52,5% of sportsmen-weightlifters [6]. During comparative analysis of AH frequency rate depending on the kind of sport normal AP level was registered among 11 sportsmen (42,2%) of acyclic kinds of sport, high arterial pressure was among 15 sportsmen (57,7%). Among sportsmen, who go in for single combats, normal AP had 68 (62,4%) people,
high arterial pressure had 41 (37,6%) people (table 1). At the same time, no statistically valid dependence of arterial hypertension on a kind of sport was stated (x2=3,48, df=1, p=0,062).
The frequency of I/D genotypes of polymorphism of ACE gene among the examined sportsmen submits to Hardy-Weinberg balance (II - 43,7%, ID - 39,3%, DD - 17,0%, x2=3,23, df=1, p=0,072). Among people with a high level of AP carriership of D allele was 67,8% vs 48,1% of people with normal AP level. Carriership of DD genotype was revealed among 25% of sportsmen with a high level of AP and 11,4% among people with normal AP level (table 2). Statistical analysis showed, that chances ratio of D allele carriership among the examined sportsmen with arterial hypertension is twice higher, than of I allele (95% Di Osh 1,1 -3,7). At the same time, relative chance to have homozygous genotype DD is 2,5 times higher (95% Di Osh 1,03 - 6,5) (table 2). eNOS genotypes distribution (GG - 94,1%, GT -3,7%, TT - 2,2%) deviates from Hardy-Weinberg balance(P<0.00001). On this basis statistical handling of the results according to eNOS was not held.
According to DMAP 41,5% of sportsmen had arterial hypertension. Different polymorphism of the studied genes was revealed among the examined sportsmen. People with AH had statistically valid high frequency of D allele of ACE gene (46,4%, vs 29,7%), then people with normal AP level (p=0,0075). It should be noted that D allele and DD genotype carriers have twice and 2,5 times higher chances to have AH. CONCLUSION
Thus, ah development among sportsmen in Yakut population doesn't depend on a kind of sport and sportsmanship. The received results prove the influence of polymorphism of ACE gene on the level of AP among young sportsmen of Yakut nationality, which corresponds with the results of other research works.
References
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Author's information:
Mestnikova E.N. - Center for Sports Medicine and Rehabilitation of the Sakha Republic (Yakutia) Higher Sports Skills School, 677013, Russia, Yakutsk, Oyunskiy str., House 26, e-mail: katemestnikova@mail.ru
Makharova N.V. - Doctor of Medical Sciences, 1Center for Sports Medicine and Rehabilitation of the Sakha Republic (Yakutia) Higher Sports Skills School, 677013, Russia, Yakutsk, Oyunskiy str., House 26, e-mail: katemestnikova@mail.ru
Zakharova F.A. - Doctor of Medical Sciences, Professor, Medical Institute North-Eastern Federal University Named After M.K. Ammosov, 677013, Russia, Yakutsk, Oyunskiy str., House 27 Akhmetov I.I. - Doctor of Medical Sciences, Kazan State Medical University, 420012, Russia, Kazan, Butlerova str., House 49, e-mail: katemestnikova@,mail.ru
Pinigina I.A. — Candidate of Medical Sciences1Center for Sports Medicine and Rehabilitation of the Sakha Republic (Yakutia) Higher Sports Skills School, 677013, Russia, Yakutsk, Oyunskiy str., House 26, e-mail: katemestnikova@,mail.ru
Appendix 1
Table 1 - Frequency of arterial hypertension among sportsmen of different kinds of sport
Cyclic kinds of sport (n=26) Combat sports (n=109) P
Normal AP (n=79) 11 (42,2%) 68 (62,4%) X=3,48, df=1, p=0,062
High normal AP (n=56) 15 (57,7%) 41 (37,6%)
Table 2 - Frequency and percentage of carriership of I/D alleles, polymorphism of ACE gene
among sportsmen with different AP level
Indices
Normal AP (n=79)
High normal AP (n=56)
Genotypes n % n %
II 41 51,9 18 32,1
ID 29 36,7 24 42,9
DD 9 11,4 14 25,0
Frequency of the allele, % % of carriership Frequency of the allele, % % of carriership
I 70,3 88,6 53,6 75,0
D 29,7 48,1 46,4 67,8
Chi square test with Yates' correction (frequency of alleles comparison) /2=7,15, df=1, p=0,0075
Bilateral Fisher's test 0,007
Chances ratio 2,05
95% DI Osh 1,2 - 3,4
n % n %
DD genotype carriership 9 11,4 14 25,0
Other genotypes carriership 70 88,6 42 75,0
Chi square test with Yates' correction X2=3,4, df=1, p=0,0658
Bilateral Fisher's test 0,061
Chances ratio 2,6
95% DI Osh 1,03 - 6,5
Appendix 2
■ normal level of AP
■ high AP
Picture 1 Prevalence of AH among the examined sportsmen
