Genome-Wide Association Study Reveals a Novel Association Between MYBPC3 Gene Polymorphism, Endurance Athlete Status, Aerobic Capacity and Steroid Metabolism.
| Autor: | Al-Khelaifi F; Anti-Doping Laboratory Qatar, Doha, Qatar.; UCL-Medical School, London, United Kingdom., Yousri NA; Department of Genetic Medicine, Weill Cornell Medicine-Qatar, Qatar-Foundation, Doha, Qatar.; Department of Computer and Systems Engineering, Alexandria University, Alexandria, Egypt., Diboun I; College of Health and Life Sciences, Hamad Bin Khalifa University, Doha, Qatar., Semenova EA; Department of Molecular Biology and Genetics, Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency, Moscow, Russia.; Department of Biochemistry, Kazan Federal University, Kazan, Russia., Kostryukova ES; Department of Molecular Biology and Genetics, Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency, Moscow, Russia., Kulemin NA; Department of Molecular Biology and Genetics, Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency, Moscow, Russia., Borisov OV; Department of Molecular Biology and Genetics, Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency, Moscow, Russia.; Institute for Genomic Statistics and Bioinformatics, University Hospital Bonn, Bonn, Germany., Andryushchenko LB; Department of Physical Education, Plekhanov Russian University of Economics, Moscow, Russia., Larin AK; Department of Molecular Biology and Genetics, Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency, Moscow, Russia., Generozov EV; Department of Molecular Biology and Genetics, Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency, Moscow, Russia., Miyamoto-Mikami E; Graduate School of Health and Sports Science, Juntendo University, Chiba, Japan., Murakami H; Department of Physical Activity Research, National Institutes of Biomedical Innovation, Health and Nutrition, Tokyo, Japan., Zempo H; Graduate School of Health and Sports Science, Juntendo University, Chiba, Japan.; Faculty of Health and Nutrition, Tokyo Seiei College, Tokyo, Japan., Miyachi M; Department of Physical Activity Research, National Institutes of Biomedical Innovation, Health and Nutrition, Tokyo, Japan., Takaragawa M; Graduate School of Health and Sports Science, Juntendo University, Chiba, Japan., Kumagai H; Graduate School of Health and Sports Science, Juntendo University, Chiba, Japan.; Japanese Society for the Promotion of Science, Tokyo, Japan., Naito H; Graduate School of Health and Sports Science, Juntendo University, Chiba, Japan., Fuku N; Graduate School of Health and Sports Science, Juntendo University, Chiba, Japan., Abraham D; UCL-Medical School, London, United Kingdom., Hingorani A; UCL-Medical School, London, United Kingdom., Donati F; Laboratorio Antidoping, Federazione Medico Sportiva Italiana, Rome, Italy., Botrè F; Laboratorio Antidoping, Federazione Medico Sportiva Italiana, Rome, Italy., Georgakopoulos C; Anti-Doping Laboratory Qatar, Doha, Qatar., Suhre K; Department of Physiology and Biophysics, Weill Cornell Medicine-Qatar, Qatar-Foundation, Doha, Qatar., Ahmetov II; Department of Molecular Biology and Genetics, Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency, Moscow, Russia.; Department of Physical Education, Plekhanov Russian University of Economics, Moscow, Russia.; Research Institute for Sport and Exercise Sciences, Liverpool John Moores University, Liverpool, United Kingdom.; Laboratory of Molecular Genetics, Kazan State Medical University, Kazan, Russia., Albagha O; College of Health and Life Sciences, Hamad Bin Khalifa University, Doha, Qatar.; Center for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, The University of Edinburgh, Edinburgh, United Kingdom., Elrayess MA; Biomedical Research Institute (BRC), Qatar University, Doha, Qatar. |
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| Jazyk: | angličtina |
| Zdroj: | Frontiers in genetics [Front Genet] 2020 Jun 16; Vol. 11, pp. 595. Date of Electronic Publication: 2020 Jun 16 (Print Publication: 2020). |
| DOI: | 10.3389/fgene.2020.00595 |
| Abstrakt: | Background: The genetic predisposition to elite athletic performance has been a controversial subject due to the underpowered studies and the small effect size of identified genetic variants. The aims of this study were to investigate the association of common single-nucleotide polymorphisms (SNPs) with endurance athlete status in a large cohort of elite European athletes using GWAS approach, followed by replication studies in Russian and Japanese elite athletes and functional validation using metabolomics analysis. Results: The association of 476,728 SNPs of Illumina DrugCore Gene chip and endurance athlete status was investigated in 796 European international-level athletes (645 males, 151 females) by comparing allelic frequencies between athletes specialized in sports with high ( n = 662) and low/moderate ( n = 134) aerobic component. Replication of results was performed by comparing the frequencies of the most significant SNPs between 242 and 168 elite Russian high and low/moderate aerobic athletes, respectively, and between 60 elite Japanese endurance athletes and 406 controls. A meta-analysis has identified rs1052373 (GG homozygotes) in Myosin Binding Protein ( MYBPC3 ; implicated in cardiac hypertrophic myopathy) gene to be associated with endurance athlete status ( P = 1.43 × 10 -8 , odd ratio 2.2). Homozygotes carriers of rs1052373 G allele in Russian athletes had significantly greater VO Conclusions: This is the first report of genome-wide significant SNP and related metabolites associated with elite athlete status. Further investigations of the functional relevance of the identified SNPs and metabolites in relation to enhanced athletic performance are warranted. (Copyright © 2020 Al-Khelaifi, Yousri, Diboun, Semenova, Kostryukova, Kulemin, Borisov, Andryushchenko, Larin, Generozov, Miyamoto-Mikami, Murakami, Zempo, Miyachi, Takaragawa, Kumagai, Naito, Fuku, Abraham, Hingorani, Donati, Botrè, Georgakopoulos, Suhre, Ahmetov, Albagha and Elrayess.) |
| Databáze: | MEDLINE |
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