D.V. Muzhenya, Ph.D.
A.R. Tuguz, professor, Dr.Biol.
A.S. Doroshenko, associate professor, Ph.D.
K.A. Rudenko, postgraduate student
Adyghe State University, Maikop

Keywords: MTHFR gene, SNP-, Val222 / 222 Ala polymorphisms, physical working capacity, PWC170, qualified athletes, sports medicine.

Introduction. The process of qualification and training of elite athletes in modern conditions can be enhanced by using high technologies, based on molecular genetic methods of identification of human capabilities. The main area of this research is allocating informative markers that predispose to specific kinds of sports activity.

The most promising direction in the evaluation of physical working capacity is the study of Val222 Ala (rs1801133) genetic polymorphisms in methylenetetrahydrofolate reductase (MTHFR), involved in the processes of DNA methylation, epigenetic variability and maintaining of the functional status of key genes involved in the differentiation and growth of muscle fibers (size, number, type of muscle fibers, etc.), development of athletes’ capabilities. Disturbance of remethylation processes, caused by the MTHFR deficiency as a result of point mutations (single-nucleotide polymorphism or SNP) of the gene may lead to a disturbance of homocysteine metabolism, development of atherosclerosis, progression of coronary heart disease (CHD), thrombosis and other pathological conditions developing on the background of intense physical loads.

I.I. Akhmetov (2011) detected the correlation between 222Val allele of the MTHFR gene and the cross-section (CS) of muscle fibers associated with DNA hypomethylation. While estimating the allele and genotype frequencies in dependence to athletes' skill level, it was determined that in the groups of candidate masters of sport (CMS), masters of sport (MS) and world-class athletes (WCA) the 222Val allele frequencies increased and amounted to 26.2:27.4:30.3:34.2 % respectively [12].

The purpose of the study was to examine the associations of Val222/222Ala (C667/667T) polymorphisms in the MTHFR gene with the level of physical working capacity according to the findings of the stress test (PWC170) and body mass index (BMI), as well as with the risk of development of cardiovascular diseases (CVD) in qualified athletes of the Republic of Adygea.

Materials and methods. The study involved 59 males, including 29 qualified athletes (10 football players, 10 basketball players, 9 track and field athletes) aged 18-25 years (mean age - 22.7±3.45) and 30 in-patients aged 44-65 years (mean age - 52.7±9.45), with coronary (n=20) and peripheral (n=10) atherosclerosis, subjected to standard screening and in-depth instrumental examination on the premises of the Adyghe Republican Clinical Hospital (Maikop city, the Republic of Adygea).

Distribution of the genotype frequencies in the samplings was examined for compliance with the Hardy-Weinberg equilibrium. The statistically significant differences (р<0.05) were determined using Fisher's non-parametric method, χ² (chi-square) for 2x2 contingency tables corrected by Yeats for steadiness and with calculation of odds-ratio (OR), 95% confidence interval (95% CI), the correlation analysis was conducted using the Spearman's non-parametric method within the program SPSS Statistics 17.0.

Results and discussion. To confirm the role of genetic polymorphisms in the development of physical working capacity in the group of qualified athletes of the Republic of Adygea, we studied the correlation of Ala222/222Val polymorphisms in the MTHFR gene with the indices of PWC₁₇₀ and BMI (Tables 1, 2).

Table 1. MTHFR genotype frequencies and indices of PWC₁₇₀ in qualified athletes

Note. Here and in Table 2: р – statistically significant differences in genotypes; r – correlation level; * – significant correlation dependences (р≤0.05).

A statistically significant increase in the indices of PWC₁₇₀ (274±12.7 W) was observed in the group of qualified basketball players with the heterozygous genotype Ala222Val in the MTHFR gene compared with the homozygous genotype Ala222Ala (245±7.1 W), the correlation coefficient equaled r=+0.86 (р≤0.05) (refer to Table 2).

Тable 2. Correlation of MTHFR genotypes with BMI in the examined groups

According to the data in Table 2, we detected a positive correlation between the values of BMI and polymorphisms in the MTHFR gene (r=+0.78; р<0.05) for qualified basketball players. Carriers of the heterozygous genotype Ala222Val are characterized by higher (р<0.05) values of BMI (23.21±0.94) compared with the Ala222Ala «normal» homozygotes (20.67±0.58) (refer to Table 2).

Basing on the above data, we can assume that the Ala222Val genotype is associated with the increase of working capacity of qualified basketball players of the Republic of Adygea. This correlates with the data obtained by I.I. Akhmetov (2011) and I. Terruzzi (2011), which reflects the mechanism of influence of the polymorphic variant of 222Val (the Ala222Val and Val222Val genotypes) in the MTHFR gene on DNA hypomethylation and activation of the factors of proliferation, myoblast differentiation, that contribute to muscle mass gain and, as a result, an increase of general working capacity.

Over the last years, search for the markers of prenosological diagnostics of genetic predisposition, or the so-called CC3 development predicators in qualified athletes on the background of intense physical loads, is an up-to-date trend of sports medicine research. Point mutations (SNP) of the MTHFR gene may lead to development of atherogenesis and progression of the cardiovascular disease continuum, like CHD, thromboses and other pathological conditions typical for failure of adaptation mechanisms on the background of intense physical loads.

Consequently, for the purpose of the present study we analyzed the distribution of frequencies of Ala222/222Val polymorphisms in the MTHFR gene in the groups of patients with CC3 and qualified basketball players, football players and track and field athletes - CMS, MS, WCA.

Ala222Val polymorphism in the MTHFR gene is not associated with the CC3 development risk in the residents of the Adyghe Republic, which is confirmed by the absence of statistically significant differences in distribution of the allele frequencies Ala222/222Val and genotype variants (AlaAla, AlaVal, ValVal) in methylenetetrahydrofolate reductase in the examined groups.

No ethnogenetic differences in the distribution of the polymorphic locus Ala222Val in methylenetetrahydrofolate reductase were observed between qualified athletes and patients with CC3.

According to I. Terruzzi et al. (2011), I.I. Akhmetov (2011), and also basing on the in-house study results, we determined that Val222Ala polymorphism being studied is correlated with the indices of physical working capacity of qualified athletes of the Republic of Adygea and is a viable marker for further studies (the correlation coefficient between the compared indices is above the average: r=+0.78 at р<0.05).

The obtained data, combined with instrumental sub-studies of the functional status of the body, can be vital for development of the criteria of evaluation of the body’s potentialities, which will ensure an improvement of the qualification process in elite sports, as well as reduce the CC3 risk in qualified athletes.

Conclusions. The heterozygous genotype Ala222Val in the MTHFR gene is a molecular genetic marker of physical working capacity, and it correlates with PWC₁₇₀ in the group of qualified basketball players (r=+0.78; р<0.05). In qualified athletes of the Republic of Adygea, Ala222/222Val polymorphisms in the MTHFR gene are not associated with the ССЗ development risk.

References

1. Lekontsev, E.V. Some genetic indicators of human physical abilities: abstract of Ph.D. thesis / E.V. Lekontsev. Kol'tsov Institute of Developmental Biology, Russian Academy of Sciences. – Мoscow, 2007. – 22 P. (In Russian)
2.  Lekontsev, E.V. Molecular genetic analysis of association of polymorphic variants of the genotype of ACE gene and level of maximum oxygen consumption in twins / E.V. Lekontsev, O.V. Gumerova, E.V. Vorob'yova et al. // Meditsinskaya genetika. – 2005. – P. 4. – № 5. – P. 218. (In Russian)
3. Muzhenya, D.V. New approach to preclinical diagnosis of cardiovascular disease in elite athletes of the Republic of Adygea / D.V. Muzhenya, A.R. Tuguz, A.S. Doroshenko, E.N. Anokhina et al. // Teoriya i praktika fizicheskoy kul'tury. – 2013. – № 8. – P. 30–33. (In Russian)
4. Pushkarev, V.P. Assessment of genetic perspectives of athletes in team sports / V.P. Pushkarev, L.V. Rakhmanina, E.V. Lekontsev et al. //Teoriya i praktika fizicheskoy kul'tury. - 2010. - №1.- P. 36-39. (In Russian)
5. Rogozkin, V.A. Genetic markers of human physical working capacity / V.A. Rogozkin et al. // Teoriya i praktika fizicheskoy kul'tury. – 2000. – № 12. – P. 34–36. (In Russian)

Corresponding author: zabolotniy-tol1@yandex.ru