Screening and gene analysis for the protection from muscle damage by statin drugs

2012 Fiscal Year Final Research Report

• Project/Area Number: 21390179
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Laboratory medicine
• Research Institution: Gifu University
• Principal Investigator: SEISHIMA Mitsuru 岐阜大学, 医学系研究科, 医学系研究科 (10171315)
• Co-Investigator(Kenkyū-buntansha): ITO Hiroyasu 岐阜大学, 大学院・医学系研究科, 講師 (80373075) ; OSAWA Yousuke 岐阜大学, 大学院・医学系研究科, 助教 (60447787) ; MORI Ichiro 岐阜大学, 大学院・医学系研究科, 助教 (40444327) ; KANAMORI Hiromitsu 岐阜大学, 医学部附属病院, 助教 (20456502) ; SAITO Kuniaki 京都大学, 医学研究科, 教授 (80262765)
• Project Period (FY): 2009 – 2012
• Keywords: スタチン製剤 / 筋障害 / 細胞内カルシウム / リアノジン受容体 / 遺伝子解析 / フローサイトメトリー

Research Abstract

We determined Ca2+increase in CD19+ cells by FCM. Rosuvastatin user patients with CK elevation showed a significant increase in Ca2+ within CD19+ cells compared with that in patients without CK elevation. Out of 18 patients with an elevated Ca2+, we found out one case with a mutation in exon 34 in RyR1 gene and two cases with amutation in exon 4 in CPTII gene. These findings show that this method is useful for the screening of a mutation in genes that relate to Ca2+transport and for the prediction of muscle damage by statins.

Research Products

• [Journal Article] Resveratrol reverses remodeling in hearts with large, old myocardial infarctions through enhanced autophagy-activating AMP kinase pathway (2013)
  • Author(s): Kanamori H, Takemura G, Goto K, Tsujimoto A, Ogino A, Takeyama G, Kawaguchi T, Watanabe T, Morishita K, Kawasaki M, Mikami A, Fujiwara T, Fujiwara H, Seishima M, Minatoguchi S.
  • Journal Title: Am J Pathol Volume: 182 Pages: 701-13
  • DOI: DOI:10.1016/j.ajpath.2012.11.009
  • Peer Reviewed
• [Journal Article] L-tryptophan-mediated enhancement of susceptibility to nonalcoholic fatty liver disease is dependent on the mammalian target of rapamycin (2011)
  • Author(s): Osawa Y, Kanamori H, Seki E, Hoshi M, Ohtaki H, Yasuda Y, Ito H, Suetsugu A, Nagaki M, Moriwaki H, Saito K, Seishima M.
  • Journal Title: J Biol Chem Volume: 286 Pages: 34800-8
  • DOI: DOI:10.1074/jbc.M111.235473
  • Peer Reviewed
• [Journal Article] Acid sphingomyelinase regulates glucose and lipid metabolism in hepatocytes through AKT activation and AMP-activated protein kinase suppression. (2011)
  • Author(s): Osawa Y, Seki E, Kodama Y, Suetsugu A, Miura K, Adachi M, Ito H, Shiratori Y, Banno Y, Olefsky JM, Nagaki M, Moriwaki H, Brenner DA, Seishima M
  • Journal Title: FASEB J Volume: 25 Pages: 1133-44
  • DOI: DOI:10.1096/fj.10-168351
  • Peer Reviewed
• [Journal Article] Comparison of chemiluminescence enzyme immunoassay (CLEIA) with ELISA for the determination of anti-cyclic citrullinated peptide antibodies (2010)
  • Author(s): Tanaka R, Takemura M, Sato M, Yamada Y, Nakagawa T, Horibe T, Hoshi M, Ohtaki H, Ito H, Seishima M, Shimizu K.
  • Journal Title: Clin Chim Acta Volume: 411 Pages: 22-5
  • DOI: DOI:10.1016/j.cca.2009.09.032
  • Peer Reviewed
• [Journal Article] Statin-induced Ca2+release wasincreased in B lymphocytes in patients who showed elevated serum creatine kinase during statin treatment. (2009)
  • Author(s): Hattori T, Saito K, Takemura M, Ito H, Ohta H, Wada H, Sei Y, Kawamura M,Seishima M.
  • Journal Title: J Atheroscler Thromb Volume: 16 Pages: 870-7
  • URL: https://www.jstage.jst.go.jp/browse/jat
  • Peer Reviewed
• [Presentation] 脂質異常症の治療～動脈硬化予防の戦略として～ (2012)
  • Author(s): 清島 満
  • Organizer: 第59回日本臨床検査医学会学術集会(招待講演)
  • Place of Presentation: 京都市
  • Year and Date: 20121129-1202
• [Presentation] Is the measurement of Ca2+-release inCD19+ B cells stimulated by statin useful for prediction of muscle damage as a side effect? (2012)
  • Author(s): Mori I, Hattori T, Osawa Y, Kanamori H, Kajita K, Morita H, Ishizuka T, Saito K, Ito H, Seishima M
  • Organizer: 第44回日本動脈硬化学会総会・学術集会
  • Place of Presentation: 福岡市
  • Year and Date: 20120719-20
• [Presentation] 検査情報を生かすための病態情報解析医学に学ぶ. (2012)
  • Author(s): 清島 満
  • Organizer: 第4回日本臨床一般検査学会学術集会(招待講演)
  • Place of Presentation: 岐阜市
  • Year and Date: 2012-10-27
• [Presentation] Ca2+releasing effect of stains on human CD19+primary B cells. (2010)
  • Author(s): Hattori T, Saito K, Takemura M, Ito H, Ohta H, Wada H, Sei Y, Kawamura M, Seishima M
  • Organizer: 第42回日本動脈硬化学会総会・学術集会
  • Place of Presentation: 岐阜市
  • Year and Date: 2010-06-15
• [Presentation] Inhibition of acid sphingomyelinasecauses hepatic glucose intolerance and insulin resistance (2010)
  • Author(s): Osawa Y, Ito H, Suetsugu A, Nagaki M, Moriwaki H, Seishima M.
  • Organizer: DDW 2010 New Orleans
  • Place of Presentation: USA
  • Year and Date: 2010-05-03
• [Presentation] 高脂血症治療剤による培養細胞に対するCa2+放出効果の基礎的検討 (2010)
  • Author(s): 服部高幸、竹村正男、太田浩敏、 大澤陽介、金森寛充、伊藤弘康、斎藤邦明、清島 満
  • Organizer: 第49回日本臨床検査医学会東海・北陸支部総会 第320回日本臨床化学会東海・北陸支部例会 連合大会
  • Place of Presentation: 名古屋
  • Year and Date: 2010-03-14
• [Book] 標準臨床検査医 (2012)
  • Author(s): 清島 満 標準臨床検査医学(高木 康・山田康幸編)
  • Total Pages: 163-177
  • Publisher: 学医学書院, 東京
• [Book] 病理学入門 (2011)
  • Author(s): 清島
  • Total Pages: 52-66
  • Publisher: 昭和堂, 京都
• [Remarks]
  • URL: http://www1.gifu-.ac.jp/~labmed/