Do skeletal muscle fiber composition-related genetic polymorphisms predict future chronic diseases?

• Project/Area Number: 18K11057
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 59040:Nutrition science and health science-related
• Research Institution: Juntendo University
• Principal Investigator: Goto Sataro 順天堂大学, スポーツ健康科学研究科, 客員教授 (10012650)
• Co-Investigator(Kenkyū-buntansha): 熊谷 仁 順天堂大学, スポーツ健康科学部, 特任助教 (00794819) ; 福 典之 順天堂大学, スポーツ健康科学部, 先任准教授 (40392526) ; 宮本 恵里 順天堂大学, スポーツ健康科学研究科, 助教 (00793390)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 筋線維組成 / 遺伝子多型 / 生活習慣病 / 高血圧 / ACTN3 R577X / ACE I/D / 元アスリート / アスリート / 競技種目 / 運動様式 / バイオマーカー

Outline of Final Research Achievements

The aims of the present study were 1) identifying myosin heavy chain (MHC) isoforms (MHC-I, MHC-IIa, and MHC-IIx)-related genetic polymorphism in the Japanese population, and 2) examining whether skeletal muscle fiber composition-related genetic polymorphisms predict future development of chronic diseases. We observed that men with the ACTN3 RR + RX genotype showed a higher proportion of MHC-IIx than those with the ACTN3 XX genotype, and men with the ACE ID + DD genotype exhibited a higher proportion of MHC-I than those with the ACE II genotype. Furthermore, a combined genotype predicting a higher MHC-I proportion, namely XX genotype of the ACTN3 R577X and ID+DD genotype of the ACE I/D polymorphisms, exhibited a lower risk of future hypertension.

Academic Significance and Societal Importance of the Research Achievements

骨格筋の筋線維組成は、大きく「速筋線維」と「遅筋線維」に分類される。速筋線維優位のアスリートは大きな力を瞬間的に発揮する能力に優れるが、代謝性疾患や高血圧のリスクが高い可能性がある。一方、遅筋線維優位のアスリートは小さい力を長時間発揮する能力に優れ、代謝性疾患および高血圧のリスクが低いと考えられている。本研究は、ヒトが生まれながらに有する遺伝子型が筋線維組成に関連することを明らかにし、さらにこれらの遺伝子型が高血圧の発症リスクに関連することを明らかにした。これらの研究成果は、遺伝子型に基づいたアスリートの適正種目の選択や、臨床現場における個別化医療の実現に寄与する可能性を有すると考えられる。

Research Products

• [Int'l Joint Research] Liverpool John Moores University(英国)
• [Int'l Joint Research] Kazan State Medical University/Ural State University/South Ural State Medical University(ロシア連邦)
• [Int'l Joint Research] University of Southern California(米国)
• [Int'l Joint Research] The University of Auckland(ニュージーランド)
• [Journal Article] Regular aerobic exercise improves sexual function assessed by the Aging Males’ Symptoms questionnaire in adult men (2020)
  • Author(s): Kumagai Hiroshi、Myoenzono Kanae、Yoshikawa Toru、Tsujimoto Takehiko、Shimomura Kosei、Maeda Seiji
  • Journal Title: The Aging Male Volume: 12 Issue: 5 Pages: 1-8
  • DOI: 10.1080/13685538.2020.1724940
  • Peer Reviewed / Open Access
• [Journal Article] Increased expression of the mitochondrial derived peptide, MOTS-c, in skeletal muscle of healthy aging men is associated with myofiber composition (2020)
  • Author(s): D’Souza Randall F.、Woodhead Jonathan S. T.、Hedges Christopher P.、Zeng Nina、Wan Junxiang、Kumagai Hiroshi、Lee Changhan、Cohen Pinchas、Cameron-Smith David、Mitchell Cameron J.、Merry Troy L.
  • Journal Title: Aging Volume: 12 Issue: 6 Pages: 5244-5258
  • DOI: 10.18632/aging.102944
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The association of HFE gene H63D polymorphism with endurance athlete status and aerobic capacity: novel findings and a meta-analysis (2020)
  • Author(s): Semenova EA, Miyamoto-Mikami E, Akimov EB, Al-Khelaifi F, Murakami H, Zempo H, Kostryukova ES, Kulemin NA, Larin AK, Borisov OV, Miyachi M, Popov DV, Boulygina EA, Takaragawa M, Kumagai H, Naito H, Pushkarev VP, Dyatlov DA, Lekontsev EV, Pushkareva YE, Andryushchenko LB, Elrayess MA, Generozov EV, Fuku N, Ahmetov II
  • Journal Title: European Journal of Applied Physiology Volume: 120 Issue: 3 Pages: 665-673
  • DOI: 10.1007/s00421-020-04306-8
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Incremental short maximal exercise increases urinary liver‐type fatty acid‐binding protein in adults without CKD (2020)
  • Author(s): Kosaki Keisei、Kamijo‐Ikemori Atsuko、Sugaya Takeshi、Kumamoto Shota、Tanahashi Koichiro、Kumagai Hiroshi、Kimura Kenjiro、Shibagaki Yugo、Maeda Seiji
  • Journal Title: Scandinavian Journal of Medicine & Science in Sports Volume: 30 Issue: 4 Pages: 709-715
  • DOI: 10.1111/sms.13618
  • Peer Reviewed
• [Journal Article] Deterioration of sexual function is associated with central hemodynamics in adult Japanese men (2019)
  • Author(s): Kumagai Hiroshi、Yoshikawa Toru、Kosaki Keisei、Myoenzono Kanae、Maeda Seiji
  • Journal Title: Hypertension Research Volume: 43 Issue: 1 Pages: 36-44
  • DOI: 10.1038/s41440-019-0336-1
  • Peer Reviewed
• [Journal Article] Effect of sleep efficiency on salivary metabolite profile and cognitive function during exercise in volleyball athletes. (2019)
  • Author(s): Akazawa Nobuhiko, Kobayashi Naoko, Nakamura Yuki, Kumagai Hiroshi, Choi Youngju, Maeda Seiji.
  • Journal Title: European Journal of Applied Physiology Volume: 119 Issue: 10 Pages: 2215-2223
  • DOI: 10.1007/s00421-019-04205-7
  • Peer Reviewed
• [Journal Article] Role of High Physical Fitness in Deterioration of Male Sexual Function in Japanese Adult Men. (2019)
  • Author(s): Kumagai H, Yoshikawa T, Myoenzono K, Kosaki K, Akazawa N, Tanahashi K, Tagawa K, Zempo-Miyaki A, Maeda S.
  • Journal Title: American Journal of Men's Health Volume: 13 Issue: 3 Pages: 1-9
  • DOI: 10.1177/1557988319849171
  • Peer Reviewed / Open Access
• [Presentation] MOTS-c inhibits myostatin expression via PTEN-AKT-FOXO1 signaling pathway (2020)
  • Author(s): Hiroshi Kumagai, Ana Raquel Coelho, Junxiang Wan, Amy Huang, Hemal H. Mehta, Kelvin Yen, Paulo J. Oliveira, Pinchas Cohen, Su-Jeong Kim
  • Organizer: DORI’s 2020 Symposium
  • Int'l Joint Research
• [Presentation] アスリートの競技特性が将来の高血圧発症に及ぼす影響-J-Fit+ study- (2019)
  • Author(s): 熊谷仁, 染谷由希, 吉岡将輝, 宮本恵里, 崔英珠, 寶川美月, 中村美幸, 河村剛光, 鈴木宏哉, 町田修一, 内藤久士, 前田清司, 福典之
  • Organizer: 第74回日本体力医学会
• [Presentation] 宮本（三上）恵里, 染谷由希, 熊谷仁, 河村剛光, 鈴木宏哉, 内藤久士, 福典之 (2019)
  • Author(s): 筋線維組成関連遺伝子多型が高血圧発症におよぼす影響の検討-J-Fit+ study-
  • Organizer: 第74回日本体力医学会
• [Presentation] Mitochondrial-DNA-m.1382-A>C polymorphism in the MOTS-c is associated with visceral fat area and blood pressure in Japanese men. (2019)
  • Author(s): Hiroshi Kumagai, Su-Jeong Kim, Seiji Maeda, Noriyuki Fuku, Pinchas Cohen
  • Organizer: American Aging Association 48th Annual Meeting
  • Int'l Joint Research
• [Presentation] 有酸素トレーニングが老齢マウス脳内のインスリン分解酵素のS-ニトロソ化に及ぼす影響 (2019)
  • Author(s): 張碩文、篠崎昇平、柳井修一、松本（重永）綾子、中本英子、小林裕幸、金木正夫、遠藤昌吾、後藤佐多良、内藤久士
  • Organizer: 第74回日本体力医学会
• [Presentation] Biological mechanisms of aging and intervention: Later life dietary restriction and regular exercise (2019)
  • Author(s): Sataro Goto
  • Organizer: The 11th Asia/Oceania Congress of International Association of Gerontology and Geriatrics
  • Int'l Joint Research / Invited
• [Presentation] 性ホルモン関連遺伝子多型と骨格筋ミオシン重鎖アイソフォームとの関連 (2018)
  • Author(s): 熊谷仁, 飛奈卓郎, 関根紀子, 柿木亮, 都築孝允, 塩瀬圭佑, 小林裕幸, 清永明, 田中宏暁, 内藤久士, 福典之
  • Organizer: 第73回日本体力医学会
• [Presentation] Does sport discipline at a young age influence the incidence of hypertension? -J-Fit+ study- (2018)
  • Author(s): Hiroshi Kumagai, Yuki Someya, Masaki Yoshioka, Eri Miyamoto-Mikami, Youngju Choi, Yoshimitsu Kohmura, Koya Suzuki, Shuichi Machida, Hisashi Naito, Seiji Maeda, Noriyuki Fuku.
  • Organizer: The 9th Federation of Asian and Oceanian Physiological Societies Congress