References

ppan

Personalized Psychiatry and Neurology

2712-9179

V. M. Bekhterev National Medical Research Centre for Psychiatry and Neurology of the Ministry of Health of the Russian Federation (Bekhterev NMRC PN)

10.52667/2712-9179-2022-2-2-3-27

ppan-48

Research Article

REVIEW

Genetic Biomarkers of Cardiovascular and Cerebrovascular Reserves in Athletes

Balberova

O. V.

Olga V. Balberova

454091, Chelyabinsk

Tel.: +7(968)126-58-50

olga-balberova@mail.ru

Bykov

E. V.

Evgeny V. Bykov

454091, Chelyabinsk

Sidorkina

E. G.

Elena G. Sidorkina

454091, Chelyabinsk

Petrova

M. M.

Marina M. Petrova

660022, Krasnoyarsk

Shnayder

N. A.

Natalia A. Shnayder

660022, Krasnoyarsk

Saint Petersburg, 192019

+7(812)670-02-20

naschnaider@yandex.ru

The Ural State University of Physical CultureRussian FederationV. F. Voino-Yasenetsky Krasnoyarsk State Medical UniversityRussian FederationV. F. Voino-Yasenetsky Krasnoyarsk State Medical University; V.M. Bekhterev National Medical Research Centre for Psychiatry and NeurologyRussian Federation

2022

15112022

22327

2022

Balberova O.V., Bykov E.V., Sidorkina E.G., Petrova M.M., Shnayder N.A.

Данная работа распространяется под лицензией Creative Commons Attribution 4.0.

This work is licensed under a Creative Commons Attribution 4.0 License.

https://www.jppn.ru/jour/article/view/48

As the practice of modern elite sports shows, the functional capabilities of the athlete's body have almost reached their limit. Further increase in the volume and intensity of physical activity is associated with the risk of desadaptative changes in the athlete's body. It is known that in endurance sports, the cardiovascular system is the main limiting factor in achieving a high athletic result. In this regard, a promising approach is to search for molecular genetic markers associated with high functional reserve of the cardiovascular system of athletes. A personalized approach in sports practice is an effective tool for sports selection, development of personalized training pro-grams to optimize the health status and achieve high performance of an athlete, as well as for the prevention of sports traumatism. (1) Background: to conduct a systematic review of the studies of candidate genes and their single-nucleotide variants (SNVs) associated with the functioning of the cardiovascular system in cyclical sports athletes.(2) Methods: A search for publications between 2000 - 2021 in the databases SCOPUS, Web of Science, Google Scholar, PubMed, e-LIBRARY, using the key words and their combinations; (3) Conclusions: the Identification of genetic markers (SNVs and polymorphisms of the ACE, BDKRB2, CMA1B, NOS3 and VEGFA genes) associated with the functional reserve of the cardiovascular system, can help cardiologists, sports physicians and trainers in developing personalized strategies for the selection of children / teenagers and the choice of sports specializations. Such a personalized approach will increase sports performance and reduce the risk of overtraining and failure to adapt during a difficult competitive period.

sports geneticscandidate genessingle nucleotide variantpolymorphismcardiovascular systemathletes

References1

Balberova O.V., Sidorkina E.G., Koshkina K.S., Plachy J.K., Bykov E.V. Model characteristics of competition performance in terms of atletes, functional fitness. Science for Education Today. 2021; 3: 161–176. doi: http://dx.doi.org/10.15293/2658-6762.2103.09.

Varillas-Delgado D., Tellería Orriols J.J., Del Coso J. Genetic profile in genes associated with cardiorespiratory fitness in elite Spanish male endurance athletes. Genes (Basel). 2021; 12(8): 1230. doi: 10.3390/genes12081230.

Bykov E.V., Balberova O. V., Sabiryanova Е. S., Chipyshev A.V. The features of myocardial hemodinamic and vegetative homeostasis in athletes of different qualifications from cyclic sports. Human. Sport. Medicine. 2019; 19 (3): 36-45.

Karthik A.H., Riikka K. Angiogenesis and angiocrines regulating heart growth. Vascular Biology. 2020; 2(1): R93–R104. DOI: https://doi.org/10.1530/VB-20-0006.

Toru O., Hiroshi A., Atsuhiko T.N., Issei K. Angiogenesis and cardiac hypertrophy. Circulation Research. 2014; 114 (3): 565– 571. doi.org/10.1161/CIRCRESAHA.114.

McMullen J.R., Jennings G.L. Differences between pathological and physiological cardiac hypertrophy: novel therapeutic strategies to treat heart failure. Clin Exp Pharmacol Physiol. 2007;34(4):255-62. doi: 10.1111/j.1440-1681.2007.04585.x.

https://www.genecards.org/

https://www.gtexportal.org/

Ma F., Yang Y., Li X., Zhou F., Gao C., Li M., Gao L. The association of sport performance with ACE and ACTN3 genetic polymorphisms: a systematic review and meta-analysis. PLoS One. 2013; 8 (1): e54685. doi: 10.1371/journal.pone.0054685.

Silva H.H., Silva M.G., Cerqueira F., Tavares V., Medeiros R. Genomic profile in association with sport-type, sex, ethnicity, psychological traits and sport injuries of elite athletes: review and future perspectives. Journal Sports Med Phys Fitness. 2021. doi: 10.23736/S0022-4707.21.12020-1

Melián Ortiz A., Laguarta-Val S., Varillas-Delgado D. Muscle work and its relationship with ACE and ACTN3 polymorphisms are associated with the improvement of explosive strength. Genes (Basel). 2021; 12(8): 1177. doi:10.3390/genes12081177.

Puthucheary Z., Skipworth J.R., Rawal J., Loosemore M., Van Someren K., Montgomery H.E. The ACE gene and human performance: 12 years on. Sports Med. 2011; 41(6): 433-48. doi: 10.2165/11588720-000000000-00000.

Gunel T., Gumusoglu E., Hosseini M.K., Yilmazyildirim E., Dolekcap I., Aydinli K. Effect of angiotensin I-converting enzyme and α-actinin-3 gene polymorphisms on sport performance. Mol Med Rep. 2014; 9(4): 1422-6. doi: 10.3892/mmr.2014.1974.

Papadimitriou I.D., Lucia A., Pitsiladis Y.P., Pushkarev V.P., Dyatlov D.A., Orekhov E.F., Artioli G.G., Guilherme J.P., Lancha A.H. Jr., Ginevičienė V., Cieszczyk P., Maciejewska-Karlowska A., Sawczuk M., Muniesa C.A., Kouvatsi A., Massidda M., Calò C.M., Garton F., Houweling P.J., Wang G., Austin K., Druzhevskaya A.M., Astratenkova I.V., Ahmetov I.I., Bishop D.J., North K.N., Eynon N. ACTN3 R577X and ACE I/D gene variants influence performance in elite sprinters: a multicohort study. BMC Genomics. 2016; 17: 285. doi: 10.1186/s12864-016-2462-3.

Pitsiladis Y., Wang G., Wolfarth B., Scott R., Fuku N., Mikami E., He Z., Fiuza-Luces C., Eynon N., Lucia A. Genomics of elite sporting performance: what little we know and necessary advances. Br Journal Sports Med. 2013; 47 (9): 550-5. doi: 10.1136/bjsports-2013-092400.

Eynon N., Ruiz J.R., Oliveira J., Duarte J.A., Birk R., Lucia A. Genes and elite athletes: a roadmap for future research. Journal Physiol. 2011; 589(Pt 13): 3063-70. doi: 10.1113/jphysiol.2011.207035.

Morin J.B., Bourdin M., Edouard P., Peyrot N., Samozino P., Lacour J.R. Mechanical determinants of 100-m sprint running performance. Eur Journal Appl Physiol. 2012; 112(11): 3921-30. doi: 10.1007/s00421-012-2379-8.

Hanon C., Gajer B. Velocity and stride parameters of world-class 400-meter athletes compared with less experienced runners. Journal Strength Cond Res. 2009; 23(2): 524-31. doi: 10.1519/JSC.0b013e318194e071. PMID: 19209080.

Zhang B., Tanaka H., Shono N., Miura S., Kiyonaga A., Shindo M., Saku K. The I allele of the angiotensin-converting enzyme gene is associated with an increased percentage of slow-twitch type I fibers in human skeletal muscle. Clin Genet. 2003; 63(2): 139-44. doi: 10.1034/j.1399-0004.2003.00029.x.

Jones A., Montgomery H.E., Woods D.R. Human performance: a role for the ACE genotype? Exerc Sport Sci Rev. 2002; 30(4): 184-90. doi: 10.1097/00003677-200210000-00008.

Gordon S.E., Davis B.S., Carlson C.J., Booth F.W. ANG II is required for optimal overload-induced skeletal muscle hypertrophy. Am Journal Physiol Endocrinol Metab. 2001; 280(1): E150-9. doi: 10.1152/ajpendo.2001.280.1.E150.

Dautova A.Z., Shamratova V.G. Association of polimorfism CMA 1/B (G1903A) with the Index Oxygen Transport System of the Body in young men with different levels of motor activity. Samara Journal of Science. 2015; 4 (2): 74-77. doi: 10.17816/snv20152121.

Chen L.Y., Li P., He Q., Jiang L.Q., Cui C.J., Xu L., Liu L.S. Transgenic study of the function of chymase in heart remodeling. Journal Hypertens. 2002; 20(10): 2047-55. doi: 10.1097/00004872-200210000-00025.

Takai S, Jin D, Miyazaki M. Multiple mechanisms for the action of chymase inhibitors. Journal Pharmacol Sci. 2012; 118(3): 311-6. doi: 10.1254/jphs.11r11cp. Epub 2012 Feb 14. PMID: 22333480.

Wang H., Varagic J., Nagata S., Kon N.D., Ahmad S., VonCannon J.L., Wright K.N., Sun X., Deal D., Groban L., Ferrario C.M. Differential expression of the angiotensin-(1-12) / chymase axis in human atrial tissue. Journal Surg Res. 2020; 253:173- 184. doi: 10.1016/j.jss.2020.03.051.

Ahmad S., Simmons T., Varagic J., Moniwa N., Chappell M.C., Ferrario C.M. Chymase-dependent generation of angiotensin II from angiotensin-(1-12) in human atrial tissue. PLoS One. 2011; 6(12): e28501. doi: 10.1371/journal.pone.0028501.

Tojo H., Urata H. Chymase inhibition and cardiovascular protection. Cardiovasc Drugs Ther. 2013; 27(2): 139-43. doi: 10.1007/s10557-013-6450-4. PMID: 23468322.

Ferrario C.M., Ahmad S., Varagic J., Cheng C.P., Groban L., Wang H., Collawn J.F., Dell Italia L.J. Intracrine angiotensin II functions originate from noncanonical pathways in the human heart. Am Journal Physiol Heart Circ Physiol. 2016; 311(2): H404-14. doi: 10.1152/ajpheart.00219.2016.

Grenda A., Leońska-Duniec A., Cięszczyk P., Zmijewski P. Bdkrb2 gene -9/+9 polymorphism and swimming performance. Biol Sport. 2014; 31(2): 109-13. doi: 10.5604/20831862.1096047.

Saunders C.J., de Milander L., Hew-Butler T., Xenophontos S.L., Cariolou M.A., Anastassiades L.C., Noakes T.D., Collins M. Dipsogenic genes associated with weight changes during Ironman Triathlons. Hum Mol Genet. 2006; 15(20): 2980-7. doi: 10.1093/hmg/ddl240.

Williams A.G., Dhamrait S.S., Wootton P.T., Day S.H., Hawe E., Payne J.R., Myerson S.G., World M., Budgett R., Humphries S.E., Montgomery H.E. Bradykinin receptor gene variant and human physical performance. Journal Appl Physiol (1985). 2004; 96(3): 938-42. doi: 10.1152/japplphysiol.00865.2003.

Eynon N., Meckel Y., Alves A.J., Nemet D., Eliakim A. Is there an interaction between BDKRB2 -9/+9 and GNB3 C825T polymorphisms and elite athletic performance? Scand Journal Med Sci Sports. 2011; 21(6): e242-6. doi: 10.1111/j.1600-0838.2010.01261.x.

Shnayder N.A., Petrova M.M., Popova T.E., Davidova T.K., Bobrova O.P., Trefilova V.V., Goncharova P.S., Balberova O.V., Petrov K.V., Gavrilyuk O.A., et al. Prospects for the personalized multimodal therapy approach to pain management via action on NO and NOS. Molecules. 2021; 26: 2431. https://doi.org/10.3390/molecules26092431.

Dawson E.A., Sheikhsaraf B., Boidin M., Erskine R.M., Thijssen D.H.J. Intra-individual differences in the effect of endurance versus resistance training on vascular function: A cross-over study. Scand Journal Med Sci Sports. 2021; 31(8): 1683-1692. doi: 10.1111/sms.13975.

Shnayder N.A., Petrova M.M., Moskaleva P.V., Shesternya P.A., Pozhilenkova E.A., Nasyrova R.F. The role of single nucleotide variants of NOS1, NOS2 and NOS3 genes in the comorbidity of arterial hypertension and tension-type headache. Molecules. 2021; 26 (6): 1556. https://doi.org/10.3390/molecules26061556

Trefilova V.V., Shnayder N.A., Popova T.E., Balberova O.V., Nasyrova R.F. The role of NO system in low back pain chronicity. Personalized Psychiatry and Neurology. 2021; 1(1): 37-45. doi: 10.52667/2712-9179-2021-1-1-37-45

Green DJ, Maiorana A, O'Driscoll G, Taylor R. Effect of exercise training on endothelium-derived nitric oxide function in humans. Journal Physiol. 2004; 561(Pt 1): 1-25. doi: 10.1113/jphysiol.2004.068197.

Gielen S, Schuler G, Adams V. Cardiovascular effects of exercise training: molecular mechanisms. Circulation. 2010; 122(12): 1221-38. doi: 10.1161/CIRCULATIONAHA.110.939959.

Tune J.D., Gorman M.W., Feigl E.O. Matching coronary blood flow to myocardial oxygen consumption. Journal Appl Physiol. 2004; 97(1): 404-15. doi: 10.1152/japplphysiol.01345.2003.

Schuler G., Adams V., Goto Y. Role of exercise in the prevention of cardiovascular disease: results, mechanisms, and new perspectives. Eur Heart J. 2013; 34(24): 1790-9. doi: 10.1093/eurheartj/eht111.

Ashor A.W., Lara J., Siervo M., Celis-Morales C., Oggioni C., Jakovljevic D.G., Mathers J.C. Exercise modalities and endothelial function: a systematic review and dose-response meta-analysis of randomized controlled trials. Sports Med. 2015; 45(2): 279-96. doi: 10.1007/s40279-014-0272-9.

Shi J., Liu S., Guo Y. et al. Association between eNOS rs1799983 polymorphism and hypertension: a meta-analysis involving 14,185 cases and 13,407 controls. BMC Cardiovasc Disord. 2021; 21(385). https://doi.org/10.1186/s12872-021-02192-2.

Saunders C.J., Xenophontos S.L., Cariolou M.A., Anastassiades L.C., Noakes T.D., Collins M. The bradykinin beta 2 receptor (BDKRB2) and endothelial nitric oxide synthase 3 (NOS3) genes and endurance performance during Ironman Triathlons. Hum Mol Genet. 2006; 15(6): 979-87. doi: 10.1093/hmg/ddl014.

Balberova, O.V.; Bykov, E.V.; Shnayder, N.A.; Petrova, M.M.; Gavrilyuk, O.A.; Kaskaeva, D.S.; Soloveva, I.A.; Petrov, K.V.; Mozheyko, E.Y.; Medvedev, G.V.; Nasyrova R.F. The “angiogenic switch” and functional resources in cyclic sports athletes. Int. Journal Mol. Sci. 2021; 22: 6496. doi: 10.3390/ijms22126496.

Varet J., Douglas S.K., Gilmartin L., Medford A.R., Bates D.O., Harper S.J., Millar A.B. VEGF in the lung: a role for novel isoforms. Am Journal Physiol Lung Cell Mol Physiol. 2010; 298(6): L768-74. doi: 10.1152/ajplung.00353.2009.

Vinnichuck J.D., Gunina L.M. Vascular endothelial growth factor during physical loads with different mechanism of energy's providing of muscular work]. Physiological Journal. 2015; 61(1): 63-71. doi: 10.15407/fz61.01.063.

Watson C.J., Webb N.J., Bottomley M.J., Brenchley P.E. Identification of polymorphisms within the vascular endothelial growth factor (VEGF) gene: correlation with variation in VEGF protein production. Cytokine. 2000; 12(8): 1232-5. doi: 10.1006/cyto.2000.0692.

Akhmetov I.I., Khakimullina A.M., Popov D.V., Missina S.S., Vinogradova O.L., Rogozkin V.A. Polymorphism of the vascular endothelial growth factor gene (VEGF) and aerobic performance in athletes. Human Physiology. 2008; 34 (4): 97-101.

Braile M., Marcella S., Cristinziano L., Galdiero M.R., Modestino L., Ferrara A.L., Varricchi G., Marone G., Loffredo S. VEGF-A in cardiomyocytes and heart diseases. Int Journal Mol Sci. 2020; 21(15): 5294. doi: 10.3390/ijms21155294.

Giordano F.J., Gerber H.P., Williams S.P., VanBruggen N., Bunting S., Ruiz-Lozano P., Gu Y., Nath A.K., Huang Y., Hickey R., Dalton N., Peterson K.L., Ross J. Jr., Chien K.R., Ferrara N. A cardiac myocyte vascular endothelial growth factor paracrine pathway is required to maintain cardiac function. Proc Natl Acad Sci U S A. 2001; 98(10): 5780-5. doi: 10.1073/pnas.091415198.

Semenza G.L. Hypoxia-inducible factor 1 and cardiovascular disease. Annu Rev Physiol. 2014; 76:39-56. doi: 10.1146/annurev-physiol-021113-170322.

Shen J., Xie Y., Liu Z., Zhang S., Wang Y., Jia L., Wang Y., Cai Z., Ma H., Xiang M. Increased myocardial stiffness activates cardiac microvascular endothelial cell via VEGF paracrine signaling in cardiac hypertrophy. Journal Mol Cell Cardiol. 2018; 122: 140-151. doi: 10.1016/j.yjmcc.2018.08.014.

Rose B.A., Yokota T., Chintalgattu V., Ren S., Iruela-Arispe L., Khakoo A.Y., Minamisawa S., Wang Y. Cardiac myocyte p38α kinase regulates angiogenesis via myocyte-endothelial cell cross-talk during stress-induced remodeling in the heart. Journal Biol Chem. 2017; 292(31): 12787-12800. doi: 10.1074/jbc.M117.784553.

Huey KA. Potential roles of vascular endothelial growth factor during skeletal muscle hypertrophy. Exerc Sport Sci Rev. 2018; 46 (3): 195-202. doi: 10.1249/JES.0000000000000152.

Schmaier A.H. The kallikrein-kinin and the renin-angiotensin systems have a multilayered interaction. Am Journal Physiol Regul Integr Comp Physiol. 2003; 285(1): R1-13. doi: 10.1152/ajpregu.00535.2002.

La Montagna R., Canonico R., Alfano L., Bucci E., Boffo S., Staiano L., Fulco B., D'Andrea E., De Nicola A., Maiorano P., D'Angelo C., Chirico A., De Nicola A., Giordano A. Genomic analysis reveals association of specific SNPs with athletic performance and susceptibility to injuries in professional soccer players. Journal Cell Physiol. 2020; 235(3): 2139-2148. doi: 10.1002/jcp.29118.

Linde E.V., Akhmetov I.I., Ordzhonikidze Z.G. Genetic factors and the formation of left ventricular myocardial hypertrophy in highly qualified athletes. Science and Sport: Modern Trends. 2014; 2 (3). URL: https://cyberleninka.ru/article/n/geneticheskie-faktory-i-formirovanie-gipertrofii-miokarda-levogo-zheludochka-u-vysokokvalifitsirovannyh-sportsmenov.

Dietze G.J., Wicklmayr M., Rett K., Jacob S., Henriksen E.J. Potential role of bradykinin in forearm muscle metabolism in humans. Diabetes. 1996; 45(1): 110–114.

Shen W, Zhang X, Zhao G, Wolin MS, Sessa W, Hintze TH. Nitric oxide production and NO synthase gene expression contribute to vascular regulation during exercise. Med Sci Sports Exerc. 1995; 27(8): 1125-34. PMID: 7476056.

Tobina T., Michishita R., Yamasawa F., Zhang B., Sasaki H., Tanaka H., Saku K., Kiyonaga A. Association between the angiotensin I-converting enzyme gene insertion/deletion polymorphism and endurance running speed in Japanese runners. Journal Physiol Sci. 2010; 60(5): 325-30. doi: 10.1007/s12576-010-0100-4. Epub 2010 Jun 24. PMID: 20574690.

Nazarov I.B., Woods D.R., Montgomery H.E., Shneider O.V., Kazakov V.I., Tomilin N.V., Rogozkin V.A. The angiotensin converting enzyme I/D polymorphism in Russian athletes. Eur Journal Hum Genet. 2001; 9(10): 797-801. doi: 10.1038/sj.ejhg.5200711. PMID: 11781693.

Rankinen T., Pérusse L., Gagnon J., Chagnon Y.C., Leon A.S., Skinner J.S., Wilmore J.H., Rao D.C., Bouchard C. Angiotensin-converting enzyme ID polymorphism and fitness phenotype in the HERITAGE Family Study. Journal Appl Physiol. 2000; 88(3): 1029-35. doi: 10.1152/jappl.2000.88.3.1029. PMID: 10710400.

Tsianos G., Sanders J., Dhamrait S., Humphries S., Grant S., Montgomery H. The ACE gene insertion/deletion polymorphism and elite endurance swimming. Eur Journal Appl Physiol. 2004; 92(3): 360-2. doi: 10.1007/s00421-004-1120-7. Epub 2004 May 8. PMID: 15138837.

Shenoy S., Tandon S., Sandhu J., Bhanwer A.S. Association of Angiotensin Converting Enzyme gene Polymorphism and Indian Army Triathletes Performance. Asian Journal Sports Med. 2010; 1(3): 143-50. doi: 10.5812/asjsm.34855. PMID: 22375202; PMCID: PMC3289177.

Costa A.M., Silva A.J., Garrido N.D., Louro H., de Oliveira R.J., Breitenfeld L. Association between ACE D allele and elite short distance swimming. Eur Journal Appl Physiol. 2009; 106(6): 785-90. doi: 10.1007/s00421-009-1080-z. Epub 2009 May 21. PMID: 19458960.

Ahmetov I.I., Williams A.G., Popov D.V., Lyubaeva E.V., Hakimullina A.M., Fedotovskaya O.N., Mozhayskaya I.A., Vinogradova O.L., Astratenkova I.V., Montgomery H.E., Rogozkin V.A. The combined impact of metabolic gene polymorphisms on elite endurance athlete status and related phenotypes. Hum Genet. 2009; 126(6): 751-61. doi: 10.1007/s00439-009-0728-4. PMID: 19653005.

The authors declare that there are no conflicts of interest present.