Electrocardiographic values associated with Serpain (PAI-1) gene mutation sensitivity in young athletes for forecasting cardiovascular disorders

Introduction . One of the most important issues of sports medicine and physiology is the choice of selection criteria for the children, able to cope with intense psycho-emotional and physical loads and to demonstrate significant sports results without damage to health. However, there is a tendency for health deterioration not only in children and adolescents, but also in persons involved in sports [2, 5]. The examination of young athletes revealed cardiac rhythm and conduction disorders [1, 2]. Some professional adolescent athletes demonstrated a significant increase in the total number of hypertensive, dystonic, and adverse reactions. This proves the presence of expressed functional disorders in regulatory systems and low adaptation capacities [3].

The prevalence/incidence of sudden death in young competitive athletes due to cardiovascular diseases has become an important part of the debate over the most effective and applicable preparticipation screening strategies for this population [10].

According to the data provided by M. Dennis et all (2018), from 15 young athletes’ deaths, 5 (33 %) were of an arrhythmogenic or presumed arrhythmic character, and 5 (33 %) occurred due to inherited cardiomyopathies (2 hypertrophic cardiomyopathies, 3 arrhythmogenic right ventricular cardiomyopathies) [8].

In the prognosis of cardiovascular diseases, special importance is to be paid to the risk factors of an atherosclerosis [12] and venous thromboembolism associated with a birth defect – mutations in the genes encoding anticoagulants [9]. According to the results of the study [6] dedicated to the frequency of prothrombin mutation, Leiden mutation, and T/T variation of rs 1801133 MTHFR gene in juniors and athletes, these parameters either did not differ, or were slightly higher than in the control group.

The comprehensive analysis of genetic polymorphisms in fibrinolysis and blood coagulation systems, as well as the analysis of the genes of folate cycle and platelet adhesion indicate a possible risk for athletes, which exists due to increased thrombosis. A possible negative effect may be a mutation of SERPINE PAI 1 gene, which can cause sudden death or acute myocardial infarction due to the risk of thromboembolism. This is demonstrated that the risk of venous thrombosis increases only in persons with protein S deficiency and homozygous for 4G allele. For the heterozygous type of this polymorphism (4G/5G), the risk of cardiovascular disease slightly increases.

the basis of informed consent with the help of 12-channel certified SENSITEG 1003 equipment after 5 min rest in a horizontal position.

To assess SERPINE1 (PAI-1) gene mutation, we took blood from the ulnar vein. Genotype determination was carried out with the help of polymerase chain reaction using REALTIME DNA-technologies. Statistical processing of the results was performed by means of SPSS v. 23.0 for Windows using Fisher's F-test to test the hypothesis about the equality of numerical characteristics in data distributions.

The analysis of ECG parameters when comparing the relative values of SERPINE1 (PAI-1) gene variants distribution revealed no differences depending on the athletes' gender.

Research results. Table 1 demonstrates ECG intervals, heart rate, and alpha angle values for young athletes.

Table 1

Distribution of young athletes, depending on gender and the results of ECG contour analysis, %

		P, ms	PQ, ms	QRS, ms	QT, ms	Beats per minute	Alpha angle, degrees
Girls (n = 93)	< N	4,3	21,3	–	–	52,1	63,8
	N	50,0	74,4	44,7	66,0	44,7	36,2
	> N	45,7	4,3	55,3	34,0	3,2	–
Boys (n = 107)	< N	1,8	8,2	–	–	42,7	46,4
	N	45,0	90,0	64,5	79,1	55,4	53,6
	> N	52,2	1,8	35,5	20,9	1,8	–

It was established that abnormal alleles of the polymorphisms studied occur with different frequency in different populations and are not always associated with the risk of cardiovascular diseases. Further genetics associated studies will help to identify genetic markers of cardiovascular diseases [4].

The importance of our study is connected with the analysis of electrocardiographic markers, associated with SERPIN (PAI-1) gene mutation, and their informative value in the prognosis of cardiovascular accidents in adolescents, involved in sports.

Aim . The article deals with establishing the sensitivity of electrocardiographic values, associated with SERPAIN (PAI-1) gene mutation, in young athletes and forecasting cardiovascular accidents.

Materials and methods . We examined 200 athletes from national teams, including 107 boys aged 14.95 ± 1.57 and 93 girls aged 15.04 ± 1.67. ECG registration was performed on

The expected results in both groups are the decrease of heart rate values and the increase of QRS interval, which is more pronounced in girls. P interval prolongation was found in almost a half of the subjects regardless of gender; QT interval prolongation was more typical in the group of girls (13.1 %). In girls, alpha angle decreased by 17.4 % in comparison with boys.

We revealed rhythm and conduction disorders in the group of young athletes: bradycardia in 22 (10.7 %) persons, tachycardia in 14 (6.8 %) athletes, incomplete right and left bundle branch block in 16 (7.7 %), disturbance of the repolarization of the left ventricle in 5 (2.4 %) [7]. These features of ECG values are connected with adaptive processes in the regulatory mechanisms of subjects under increased physical loads.

In order to assess the effect of SERPINE (PAI-1) gene polymorphism on ECG intervals duration, heart rate, and alpha angle values, athletes of both groups were divided into 3 subgroups depending on genotypes (Table 2).

Table 2

Distribution of young athletes with SERPINE1 (PAI-1) genotype, depending on the results of ECG contour analysis, %

Value	Variant	Boys (n = 107)			Girls (n = 93)
		4G/4G n = 12	5G/4G n = 59	5G/5G n = 36	4G/4G n = 30	5G/4G n = 41	5G/5G n = 22
P	<	8,3	1,7	–	6,7	4,9	–
	N	41,7	33,9	61,1	53,3	43,9	54,5
	>	50,0	64,4	38,9	40,0	51,2	45,5
PQ	<	8,3	10,2	5,6	23,3	24,4	13,6
	N	83,3	91,5	97,2	80,0	70,7	77,3
	>	8,3	–	2,8	–	4,9	9,1
QRS	N	50,0	32,2	36,1	60,0	34,1	40,9
	>	50,0	69,5	69,4	43,3	65,9	59,1
QT	N	75,0	83,1	80,6	60,0	65,9	68,2
	>	25,0	18,6	25,0	43,3	34,1	27,3
Heart rate	<	33,3	49,2	47,2	56,7	58,5	54,5
	N	50,0	49,2	58,3	43,3	39,0	31,8
	>	8,3	1,7	–	–	2,4	9,1
Alpha angle	<	25,0	57,6	63,9	66,7	56,1	72,7
	N	75,0	44,1	41,7	33,3	43,9	27,3

We revealed that 44.1 % and 55.1 % of female and male athletes, respectively, possess SERPINE1 (PAI-1) gene heterozygous form. Dominant genotype was revealed in 23.7 % and 33.6 % of female and male athletes, respectively, while recessive genotype was found in 32.3 % and 11.2 % of female and male participants, respectively.

In the prognosis of cardiovascular accidents, persons with SERPINE (PAI-1) gene recessive genotype are at risk. So, we analyzed the group of athletes - carriers of this genotype.

Table 2 demonstrates that prolonged QRS, P intervals, associated with SERPINE1 (PAI-1) recessive genotype, are more typical for male participants (7–10 %); in girls, prolonged QT interval can be registered 1.7 times more often than in boys. The number of female athletes with a short PQ interval almost three times exceeds the number of male athletes. Decreased HR and alpha angle values in persons with recessive genotype are 1.7 and 2.7 times more common for female athletes.

Conclusion. Screening remains contentious due to the challenges of identifying relatively rare entities amongst a healthy cohort. The imperfect diagnostic accuracy of all existing tests means that screening strategies have potential for harm through incorrect diagnoses as well as the potential for identification of important sub-clinical pathologies. The management of athletes at risk of ventricular arrhythmias and sudden cardiac death is similarly complex [11].

During the assessment of ECG intervals in both groups, we registered the predominance of persons with prolonged P intervals, QRS, QT, and reduced values of heart rate and angle alpha.

It was established that persons with SERPINE1 (PAI-1) 4G/4G genotype can practice professional sports only under the supervision of a cardiologist. If there are any injuries, the risks associated with thrombosis must be taken into account.