The purpose of this study was to investigate individually and in combination the association between the ACE (I/D), NOS3 (Glu298Asp), BDKRB2 (-9/+9), UCP2 (Ala55Val) and AMPD1 (Gln45Ter) variants with endurance performance in a large, performance-homogenous cohort of elite Polish half marathoners. The study group consisted of 180 elite half marathoners: 76 with time < 100 minutes and 104 with time > 100 minutes. DNA of the subjects was extracted from buccal cells donated by the runners and genotyping was carried out using an allelic discrimination assay with a C1000 Touch Thermal Cycler (Bio-Rad, Germany) instrument with TaqMan® probes (NOS3, UCP2, and AMPD1) and a T100™ Thermal Cycler (Bio-Rad, Germany) instrument (ACE and BDKRB2). We found that the UCP2 Ala55Val polymorphism was associated with running performance, with the subjects carrying the Val allele being overrepresented in the group of most successful runners (<100 min) compared to the >100 min group (84.2 vs. 55.8%; OR = 4.23, p < 0.0001). Next, to assess the combined impact of 4 gene polymorphisms, all athletes were classified according to the number of 'endurance' alleles (ACE I, NOS3 Glu, BDKRB2 -9, UCP2 Val) they possessed. The proportion of subjects with a high (4-7) number of 'endurance' alleles was greater in the better half marathoners group compared with the >100 min group (73.7 vs. 51.9%; OR = 2.6, p = 0.0034). These data suggest that the likelihood of becoming an elite half marathoner partly depends on the carriage of a high number of endurance-related alleles.

Department of Methodology Statistics and Informatics J Kukuczka Academy of Physical Education in Katowice Katowice Poland

Department of Sport Games Charles University Prague Prague Czech Republic

Department of Tourism and Recreation University of Physical Education and Sport Gdańsk Poland

Faculty of Medicine University of Information Technology and Management in Rzeszow Rzeszow Poland

Faculty of Physical Education University of Rzeszów Rzeszów Poland

Institute of Sports Faculty of Physical Education and Sports University of Physical Education Krakow Poland

Laboratory of Genetics Department of Gymnastics and Dance University School of Physical Education in Poznań Poznań Poland

Laboratory of Molecular Genetics Kazan State Medical University Kazan Russia

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Ahmetov II, Fedotovskaya ON. Current Progress in Sports Genomics. Adv Clin Chem. 2015;70:247. –. PubMed

Ahmetov II, Williams AG, Popov DV, Lyubaeva EV, Hakimullina AM, Fedotovskaya ON, Mozhayskaya IA, Vinogradova OL, Astratenkova IV, Montgomery HE, Rogozkin VA. The combined impact of metabolic gene polymorphisms on elite endurance athlete status and related phenotypes. Hum Genet. 2009;126:751. –. PubMed

Ahmetov II, Popov DV, Astratenkova IV, Druzhevskaia AM, Missina SS, Vinogradova OL, Rogozkin VA. The use of molecular genetic methods for prognosis of aerobic and anaerobic performance in athletes. Hum Physiol. 2009;34:338. –. PubMed

Alvarez R, Terrados N, Ortolano R, Iglesias-Cubero G, Reguero JR, Batalla A, Cortina A, Fernandez-Garcıa B, Rodrıguez C, Braga S, Alvarez V, Coto E. Genetic variation in the rennin angiotensin system and athletic performance. Eur J Appl Physiol. 2000;82:117. –. PubMed

Astrup A, Toubro S, Dalgaard LT, Urhammer SA, Sorensen TI, Pedersen O. Impact of the v/v 55 polymorphism of the uncoupling protein 2 gene on 24-h energy expenditure and substrate oxidation. Int J Obesity Related Metab Disorder. 1999;23:1030. –. PubMed

Buemann B, Schierning B, Toubro S, Bibby BM, Sørensen T, Dalgaard L, Pedersen O, Astrup A. The association between the val/ala-55 polymorphism of the uncoupling protein 2 gene and exercise efficiency. Int J Obesity Related Metab Disorder. 2001;25:467. –. PubMed

Casas JP, Cavalleri GL, Bautista LE, Smeeth L, Humphries SE, Hingorani AD. Endothelial nitric oxide synthase gene polymorphisms and cardiovascular disease: a HuGE review. Am J Epidemiol. 2006;164:921. –. PubMed

Cieszczyk P, Eider J, Ostanek M, Leońska-Duniec A, Ficek K, Kotarska K, Girdauskas G. Is the C34T polymorphism of the AMPD1 gene associated with athlete performance in rowing? Int J Sports Med. 2009;32:987. –. PubMed

Cieszczyk P, Krupecki K, Maciejewska A, Sawczuk M. The angiotensin converting enzyme gene I/D polymorphism in polish rowers. Int J Sports Med. 2009;30:624. –. PubMed

Eynon N, Hanson ED, Lucia A, Houweling PJ, Garton F, North KN, Bishop DJ. Genes for elite power and sprint performance: ACTN3 leads the way. Sports Med. 2013;43:803. –. PubMed

Eynon N, Meckel Y, Alves AJ, Nemet D, Eliakim A. Is there an interaction between BDKRB2-9/+9 and GNB3 C825T polymorphisms and elite athletic performance? Scand J Med Sci Sports. 2011;21:242. –. PubMed

Fishbein WN, Armbrustmacher VW, Griffin JL. Myoadenylate deaminase deficiency: a new T. disease of muscle. Science. 1987;200:545. –. PubMed

Fleury C, Sanchis D. The mitochondrial uncoupling protein-2: current status. Int J Biochem Cell Biol. 1999;31:1261. –. PubMed

Gayagay G, Yu B, Hambly B, Boston T, Hahn A, Celermajer DS, Trent RJ. Elite endurance athletes and the ACE I allele—the role of genes in athletic performance. Hum Genet. 1998;103:48. –. PubMed

Ginevičienė V, Jakaitiene A, Pranculis A, Milašius K, Tubelis L, Utkus A. AMPD1 rs17602729 is associated with physical performance of sprint and power in elite Lithuanian athletes. BMC Genet. 2014;15:58. PubMed PMC

Gronek P, Holdys J. Genes and physical fitness. Trends Sport Sci. 2013;20:16. –.

Gronek P, Holdys J, Konarski J, Kryściak J, Wolc A. ACE I/D genotype in Professional field hockey players. TRENDS Sport Sci. 2013;20:36. –.

Gui J, Moore JH, Williams SM, Andrews P, Hillege HL, van der Harst P, Navis G, Van Gilst WH, Asselbergs FW, Gilbert-Diamond D. A Simple and Computationally Efficient Approach to Multifactor Dimensionality Reduction Analysis of Gene-Gene Interactions for Quantitative Traits. PLoS One. 2013;8:e66545. PubMed PMC

Holdys J, Gronek P, Krysciak J, Stanisławski D. Genetics variants of uncoupling proteins-2 and-3 in relations to maximal oxygen uptake in different sports. Acta Biochim Pol. 2013;60:71. –. PubMed

Holdys J, Kryściak J, Stanisławski D, Gronek P. Polymorphism of the ACTN3 Gene in Individuals Practising Different Sports Disciplines. Biol Sport. 2011;28:101. –.

Hruskovicova H, Dzurenkova D, Selingerova M, Bohus B, Timkanicova B, Kovacs L. The angiotensin converting enzyme I/D polymorphism in long distance runners. J Sports Med Phys Fit. 2006;46:509. –. PubMed

Jelakovic B, Kuzmanic D, Milicic D. Influence of angiotensin converting enzyme (ACE) gene polymorphism and circadian blood pressure (BP) changes on left ventricle (LV) mass in competitive oarsmen. Am J Hypertens. 2000;13:182A.

Lucıa A, Gomez-Gallego F, Chicharro JL, Hoyos J, Celaya K, Cordova A, Villa C, Alonso JM, Barriopedro M. Perez M, Earnest CP. Is there an association between ACE and CKMM polymorphisms and cycling performance status during 3-week races? Int J Sports Med. 2005;26:442. –. PubMed

Massidda M, Bachis V, Corrias L, Piras F, Scorcu M, Culigioni C, Masala D, Calò CM. ACTN3 R577X polymorphism is not associated with team sport athletic status in Italians. Sports Med Open. 2015;1:6. PubMed PMC

Montgomery HE, Marshall R, Hemingway H, Myerson S, Clarkson P, Dollery C, Hayward M, Holliman DE, Jubb M, World M, Thomas EL, Brynes AE, Saeed N, Barnard M, Bell JD, Prasad K, Rayson M, Talmud PJ, Humphries SE. Human gene for physical performance. Nature. 1998;393:221. –. PubMed

Moore JH, Gilbert JC, Tsai CT, Chiang FT, Holden T, Barney N, White BC. A flexible computational framework for detecting, characterizing, and interpreting statistical patterns of epistasis in genetic studies of human disease susceptibility. J Theor Biol. 2006;241:252. –. PubMed

Morisaki T, Gross M, Morisaki H, Pongratz D, Zöllner N, Holmes EW. Molecular basis of AMP deaminase deficiency in skeletal muscle. Proc Natl Acad Sci U S A. 1992;89:6457. –. PubMed PMC

Oliveira-Paula GH, Luizon MR, Lacchini R, Fontana V, Silva PS, Biagi C, Tanus-Santos JE. Gene-Gene Interactions Among PRKCA, NOS3 and BDKRB2 Polymorphisms Affect the Antihypertensive Effects of Enalapril. Basic Clin Pharmacol. 2017;120:284. –. PubMed

Pe´russe L, Bouchard C. Endothelial nitric oxide synthase gene polymorphism and elite endurance athlete status: the Genathlete study. Scand J Med Sci Sports. 2008;18:485. –. PubMed

Popp R, Fleming I, Busse R. Pulsatile stretch in coronary arteries elicits release of endothelium- derived hyperpolarizing factor: a modulator of arterial compliance. Circ Res. 1998;82:696. –. PubMed

Rigat B, Hubert C, Corvol P, Soubrier F. PCR detection of the insertion/deletion polymorphism of the human angiotensin converting enzyme gene (DCP1) (dipeptidyl carboxypeptidase 1) Nucleic Acids Res. 1992;20:1433. PubMed PMC

Rubio JC, Martin MA, Rabadan MF, Gómez-Gallego F, San Juan AF, Alonso JM, Chicharro JL, Pérez M, Arenas J, Lucia A. Frequency of the C34T mutation of the AMPD1 gene in world-class endurance athletes: does this mutation impair performance? J Applied Physiol. 2005;98:2108. –. PubMed

Salanti G, Amountza G, Ntzani EE, Ioannidis JP. Hardy-Weinberg equilibrium in genetic association studies: an empirical evaluation of reporting, deviations, and power. Eur J Hum Genet. 2005;13:840. –. PubMed

Saunders CJ, Xenophontos SL, Cariolou MA, Anastassiades LC, Noakes TD, 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;15:979. –. PubMed

Sawczuk M, Timshina YI, Astratenkova IV, Maciejewska-Karlowska A, Leońska-Duniec A, Ficek K, Mustafina LJ, Cięszczyk P, Klocek T, Ahmetov II. The -9/+9 polymorphism of the bradykinin receptor beta 2 gene and athlete status: A study involving two European cohorts. Hum Biol. 2013;85:741. –. PubMed

Scanavini D, Bernardi F, Castoldi E, Conconi F, Mazzoni G. Increased frequency of the homozygous II ACE genotype in Italian Olympic endurance athletes. Eur J Hum Genet. 2002;10:576. –. PubMed

Sessa F, Chetta M, Petito A, Franzetti M, Bafunno V, Pisanelli D, Sarno M, Iuso S, Margaglione M. Gene polymorphisms and sport attitude in Italian athletes. Genet Test Mol Bioma. 2011;15:285. –. PubMed

Shenoy S, Tandon S, Sandhu J, Bhanwer AS. Association of converting enzyme gene polymorphism and Indian army triathletes performance. Asian Journal of Sports Medicine. 2010;1(3):143. –. PubMed PMC

Thomaes T, Thomis M, Onkelinx S, Fagard R, Matthijs G, Buys R, Schepers D, Cornelissen V, Vanhees L. A genetic predisposition score for muscular endophenotypes predicts the increase in aerobic power after training: the CAREGENE study. BMC Genet. 2011;12:84. PubMed PMC

Tsianos GI, Evangelou E, Boot A, Zillikens MC, van Meurs JBJ, Uitterlinden AG, Ioannidis JPA. Associations of polymorphisms of eight muscle- or metabolism-related genes with performance in Mount Olympus marathon runners. J Applied Physiol. 2010;108:567. –. PubMed

Tsianos G, Sanders J, Dhamrait S, Humphries S, Grant S, Montgomery H. The ACE gene insertion/deletion polymorphism and elite endurance swimming. Eur J Applied Physiol. 2004;92:360. –. PubMed

Wilkinson AV, Gabriel KP, Wang J, Bondy ML, Dong Q, Wu X, Shete S, Spitz MR. Sensation seeking genes and physical activity in youth. Genes Brain Behav. 2013;12:181. –. PubMed PMC

Williams AG, Dhamrait SS, Wootton PTE, Day SH, Hawe E, Payne JR, Myerson SG, World M, Budgett R, Humphries SE, Montgomery HE. Bradykinin receptor gene variant and human physical performance. J Applied Physiol. 2004;96:938. –. PubMed

Wu Y, Zhu Z, Fang X, Yin L, Liu Y, Xu S, Li A. The Association between NOS3 Gene Polymorphisms and Hypoxic-Ischemic Encephalopathy Susceptibility and Symptoms in Chinese Han Population. BioMed Research Int. 2016. Article ID 1957374. PubMed PMC

Zarebska A, Jastrzebski Z, Ahmetov II, Zmijewski P, Cięszczyk P, Leonska-Duniec A, Sawczuk M, Leznicka K, Trybek G, Semenova EA, Maciejewska-Skrendo A. GSTP1 c.313A>G polymorphism in Russian and Polish athletes. Physiol Genomics. 2017;49:127. –. PubMed