Genome-Wide Association Study Identifies <i>CDKN1A</i> as a Novel Locus Associated with Muscle Fiber Composition
Muscle fiber composition is associated with physical performance, with endurance athletes having a high proportion of slow-twitch muscle fibers compared to power athletes. Approximately 45% of muscle fiber composition is heritable, however, single nucleotide polymorphisms (SNP) underlying inter-indi...
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MDPI AG
2022-12-01
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| author | Ekaterina A. Semenova Hirofumi Zempo Eri Miyamoto-Mikami Hiroshi Kumagai Andrey K. Larin Rinat I. Sultanov Konstantin A. Babalyan Andrey V. Zhelankin Takuro Tobina Keisuke Shiose Ryo Kakigi Takamasa Tsuzuki Noriko Ichinoseki-Sekine Hiroyuki Kobayashi Hisashi Naito Jatin Burniston Edward V. Generozov Noriyuki Fuku Ildus I. Ahmetov |
| author_facet | Ekaterina A. Semenova Hirofumi Zempo Eri Miyamoto-Mikami Hiroshi Kumagai Andrey K. Larin Rinat I. Sultanov Konstantin A. Babalyan Andrey V. Zhelankin Takuro Tobina Keisuke Shiose Ryo Kakigi Takamasa Tsuzuki Noriko Ichinoseki-Sekine Hiroyuki Kobayashi Hisashi Naito Jatin Burniston Edward V. Generozov Noriyuki Fuku Ildus I. Ahmetov |
| author_sort | Ekaterina A. Semenova |
| collection | DOAJ |
| description | Muscle fiber composition is associated with physical performance, with endurance athletes having a high proportion of slow-twitch muscle fibers compared to power athletes. Approximately 45% of muscle fiber composition is heritable, however, single nucleotide polymorphisms (SNP) underlying inter-individual differences in muscle fiber types remain largely unknown. Based on three whole genome SNP datasets, we have shown that the rs236448 A allele located near the cyclin-dependent kinase inhibitor 1A (<i>CDKN1A</i>) gene was associated with an increased proportion of slow-twitch muscle fibers in Russian (<i>n</i> = 151; <i>p</i> = 0.039), Finnish (<i>n</i> = 287; <i>p</i> = 0.03), and Japanese (<i>n</i> = 207; <i>p</i> = 0.008) cohorts (meta-analysis: <i>p</i> = 7.9 × 10<sup>−5</sup>. Furthermore, the frequency of the rs236448 A allele was significantly higher in Russian (<i>p</i> = 0.045) and Japanese (<i>p</i> = 0.038) elite endurance athletes compared to ethnically matched power athletes. On the contrary, the C allele was associated with a greater proportion of fast-twitch muscle fibers and a predisposition to power sports. <i>CDKN1A</i> participates in cell cycle regulation and is suppressed by the miR-208b, which has a prominent role in the activation of the slow myofiber gene program. Bioinformatic analysis revealed that the rs236448 C allele was associated with increased <i>CDKN1A</i> expression in whole blood (<i>p</i> = 8.5 × 10<sup>−15</sup>) and with greater appendicular lean mass (<i>p</i> = 1.2 × 10<sup>−5</sup>), whereas the A allele was associated with longer durations of exercise (<i>p</i> = 0.044) reported amongst the UK Biobank cohort. Furthermore, the expression of <i>CDKN1A</i> increased in response to strength (<i>p</i> < 0.0001) or sprint (<i>p</i> = 0.00035) training. Accordingly, we found that <i>CDKN1A</i> expression is significantly (<i>p</i> = 0.002) higher in the m. vastus lateralis of strength athletes compared to endurance athletes and is positively correlated with the percentage of fast-twitch muscle fibers (<i>p</i> = 0.018). In conclusion, our data suggest that the <i>CDKN1A</i> rs236448 SNP may be implicated in the determination of muscle fiber composition and may affect athletic performance. |
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| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T17:50:10Z |
| publishDate | 2022-12-01 |
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| series | Cells |
| spelling | doaj.art-394761554449424ca64689a7a696385d2023-11-24T10:45:51ZengMDPI AGCells2073-44092022-12-011123391010.3390/cells11233910Genome-Wide Association Study Identifies <i>CDKN1A</i> as a Novel Locus Associated with Muscle Fiber CompositionEkaterina A. Semenova0Hirofumi Zempo1Eri Miyamoto-Mikami2Hiroshi Kumagai3Andrey K. Larin4Rinat I. Sultanov5Konstantin A. Babalyan6Andrey V. Zhelankin7Takuro Tobina8Keisuke Shiose9Ryo Kakigi10Takamasa Tsuzuki11Noriko Ichinoseki-Sekine12Hiroyuki Kobayashi13Hisashi Naito14Jatin Burniston15Edward V. Generozov16Noriyuki Fuku17Ildus I. Ahmetov18Department of Molecular Biology and Genetics, Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency, 119435 Moscow, RussiaFaculty of Health and Nutrition, Tokyo Seiei College, Tokyo 124-0025, JapanGraduate School of Health and Sports Science, Juntendo University, Chiba 270-1695, JapanGraduate School of Health and Sports Science, Juntendo University, Chiba 270-1695, JapanDepartment of Molecular Biology and Genetics, Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency, 119435 Moscow, RussiaDepartment of Molecular Biology and Genetics, Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency, 119435 Moscow, RussiaDepartment of Molecular Biology and Genetics, Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency, 119435 Moscow, RussiaDepartment of Molecular Biology and Genetics, Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency, 119435 Moscow, RussiaFaculty of Nursing and Nutrition, University of Nagasaki, Nagasaki 851-2195, JapanFaculty of Education, University of Miyazaki, Miyazaki 889-2192, JapanFaculty of Management & Information Science, Josai International University, Chiba 283-8555, JapanFaculty of Pharmacy, Meijo University, Nagoya 468-8503, JapanGraduate School of Health and Sports Science, Juntendo University, Chiba 270-1695, JapanDepartment of General Medicine, Mito Medical Center, Tsukuba University Hospital, Ibaraki 310-0015, JapanGraduate School of Health and Sports Science, Juntendo University, Chiba 270-1695, JapanResearch Institute for Sport and Exercise Sciences, Liverpool John Moores University, Liverpool L3 5AF, UKDepartment of Molecular Biology and Genetics, Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency, 119435 Moscow, RussiaGraduate School of Health and Sports Science, Juntendo University, Chiba 270-1695, JapanDepartment of Molecular Biology and Genetics, Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency, 119435 Moscow, RussiaMuscle fiber composition is associated with physical performance, with endurance athletes having a high proportion of slow-twitch muscle fibers compared to power athletes. Approximately 45% of muscle fiber composition is heritable, however, single nucleotide polymorphisms (SNP) underlying inter-individual differences in muscle fiber types remain largely unknown. Based on three whole genome SNP datasets, we have shown that the rs236448 A allele located near the cyclin-dependent kinase inhibitor 1A (<i>CDKN1A</i>) gene was associated with an increased proportion of slow-twitch muscle fibers in Russian (<i>n</i> = 151; <i>p</i> = 0.039), Finnish (<i>n</i> = 287; <i>p</i> = 0.03), and Japanese (<i>n</i> = 207; <i>p</i> = 0.008) cohorts (meta-analysis: <i>p</i> = 7.9 × 10<sup>−5</sup>. Furthermore, the frequency of the rs236448 A allele was significantly higher in Russian (<i>p</i> = 0.045) and Japanese (<i>p</i> = 0.038) elite endurance athletes compared to ethnically matched power athletes. On the contrary, the C allele was associated with a greater proportion of fast-twitch muscle fibers and a predisposition to power sports. <i>CDKN1A</i> participates in cell cycle regulation and is suppressed by the miR-208b, which has a prominent role in the activation of the slow myofiber gene program. Bioinformatic analysis revealed that the rs236448 C allele was associated with increased <i>CDKN1A</i> expression in whole blood (<i>p</i> = 8.5 × 10<sup>−15</sup>) and with greater appendicular lean mass (<i>p</i> = 1.2 × 10<sup>−5</sup>), whereas the A allele was associated with longer durations of exercise (<i>p</i> = 0.044) reported amongst the UK Biobank cohort. Furthermore, the expression of <i>CDKN1A</i> increased in response to strength (<i>p</i> < 0.0001) or sprint (<i>p</i> = 0.00035) training. Accordingly, we found that <i>CDKN1A</i> expression is significantly (<i>p</i> = 0.002) higher in the m. vastus lateralis of strength athletes compared to endurance athletes and is positively correlated with the percentage of fast-twitch muscle fibers (<i>p</i> = 0.018). In conclusion, our data suggest that the <i>CDKN1A</i> rs236448 SNP may be implicated in the determination of muscle fiber composition and may affect athletic performance.https://www.mdpi.com/2073-4409/11/23/3910DNAGWASgenotypegenetic markersmuscle fibersathletic performance |
| spellingShingle | Ekaterina A. Semenova Hirofumi Zempo Eri Miyamoto-Mikami Hiroshi Kumagai Andrey K. Larin Rinat I. Sultanov Konstantin A. Babalyan Andrey V. Zhelankin Takuro Tobina Keisuke Shiose Ryo Kakigi Takamasa Tsuzuki Noriko Ichinoseki-Sekine Hiroyuki Kobayashi Hisashi Naito Jatin Burniston Edward V. Generozov Noriyuki Fuku Ildus I. Ahmetov Genome-Wide Association Study Identifies <i>CDKN1A</i> as a Novel Locus Associated with Muscle Fiber Composition Cells DNA GWAS genotype genetic markers muscle fibers athletic performance |
| title | Genome-Wide Association Study Identifies <i>CDKN1A</i> as a Novel Locus Associated with Muscle Fiber Composition |
| title_full | Genome-Wide Association Study Identifies <i>CDKN1A</i> as a Novel Locus Associated with Muscle Fiber Composition |
| title_fullStr | Genome-Wide Association Study Identifies <i>CDKN1A</i> as a Novel Locus Associated with Muscle Fiber Composition |
| title_full_unstemmed | Genome-Wide Association Study Identifies <i>CDKN1A</i> as a Novel Locus Associated with Muscle Fiber Composition |
| title_short | Genome-Wide Association Study Identifies <i>CDKN1A</i> as a Novel Locus Associated with Muscle Fiber Composition |
| title_sort | genome wide association study identifies i cdkn1a i as a novel locus associated with muscle fiber composition |
| topic | DNA GWAS genotype genetic markers muscle fibers athletic performance |
| url | https://www.mdpi.com/2073-4409/11/23/3910 |
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