Development and the application of a comprehensive cause-analysis system for hypertriglyceridemia that is a risk factor for coronary heart disease

• Project/Area Number: 21500702
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Applied health science
• Research Institution: National Cardiovascular Center Research Institute
• Principal Investigator: TAKAGI Atsuko 独立行政法人国立循環器病研究センター, 分子薬理部, 室長 (90179416)
• Co-Investigator(Kenkyū-buntansha): IKEDA Yasuyuki 独立行政法人国立循環器病研究センター, 分子薬理部, 客員研究員 (90176107)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2010: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 高トリグリセリド血症 / リポ蛋白リパーゼ / 動脈硬化 / 心疾患 / 自己免疫性疾患 / 全身性エリテマトーデス / 全身性エリテマートデス

Research Abstract

Hypertriglyceridemia is one of the risk factors for coronary heart disease, and it is caused by an abnormality of lipoprotein lipase(LPL) that is mainly associated with catabolism of triglyceride in the circulation. In fact, we found a compound heterozygous LPL deficiency of S193R/I194T as a cause of hypertriglyceridemia in a subject with the low level of LPL activity and LPL protein. However, there was a case whose LPL gene had no abnormality in spite of the low level of LPL both activity and protein. In this case, we found an inhibitor of LPL enzyme in the patient's plasma. Detection of the inhibitor was done by a combination of the method of measuring inhibitory effect of the plasma on LPL activity and determining a typeof the immunoglobulin binding to LPL protein by Western blot method. Measurement of the inhibition of the functional LPL activity by plasma was essential for the detection of inhibitors of LPL enzyme.

Research Products

• [Journal Article] リポ蛋白質リパーゼ(LPL)・肝性トリグリセリドリパーゼ(HTGL)-広範囲血液・尿化学検査免疫学的検査ーその数値をどう読むか[第7版]IV.生化学的検査[2] A.脂質関係 (2009)
  • Author(s): 高木敦子、池田康行
  • Journal Title: 日本臨床 Volume: 67巻増刊号 Pages: 443-450
• [Journal Article] (2009)
  • Author(s): 高木敦子、池田康行
  • Journal Title: 広範囲 血液・尿化学検査 免疫学的検査-その数値をどう読むか[第7版]IV.生化学的検査[2]A.脂質関係 日本臨床67巻 増刊号(リポ蛋白質リパーゼ(LPL)・肝性トリグリセリドリパーゼ(HTGL).)
• [Presentation] 抗lipoprotein lipase抗体により高脂血症を伴ったSLEの10歳女児例 (2011)
  • Author(s): 荒木まり子、石原正行、高杉尚志、藤枝幹也、脇口宏、高木敦子、池田康行
  • Organizer: 第21回日本小児リウマチ学会総会
  • Place of Presentation: 神戸・神戸国際会議場
  • Year and Date: 2011-10-16
• [Presentation] Hypertriglyceridemia(HTG) caused by autoantibodies to lipoprotein lipase(LPL) in a patient with systemic lupus erythematosus(SLE) (2011)
  • Author(s): Atsuko Takagi, Yasuyuki Ikeda, Mariko Araki, Taku Morita, Masayuki Ishihara, Manabu Matsumoto, Hisashi Takasugi, Akihiko Maeda, Takanori Abe, Mikiya Fujieda, and Hiroshi Wakiguchi
  • Organizer: 第43回日本動脈硬化学会大会
  • Place of Presentation: 札幌・ロイトンホテル
  • Year and Date: 2011-07-16
• [Presentation] Hypertriglyceridemia (HTG) caused by autoantibodies to lipoprotein lipase (LPL) in a patient with systemic lupus erythematosus (SLE) (2011)
  • Author(s): Atsuko Takagi, Yasuyuki Ikeda, Mariko Araki, Taku Morita, Masayuki Ishihara, Manabu Matsumoto, Hisashi Takasugi, Akihiko Maeda, Takanori Abe, Mikiya Fujieda, Hiroshi Wakiguchi
  • Organizer: 第43回日本動脈硬化学会大会
  • Place of Presentation: 札幌・ロイトンホテル
  • Year and Date: 2011-07-16
• [Presentation] 高トリグリセリド血症発症の病因としてのリポ蛋白リパーゼ(LPL)に対する自己抗体産生 (2010)
  • Author(s): 高木敦子、池田康行、荒木まり子、森田拓、石原正行、松本学、高杉尚志、前田明彦、阿部孝典、藤枝幹也、脇口宏
  • Organizer: 第83回日本生化学会大会 & 第33回日本分子生物学会大会
  • Place of Presentation: 神戸ポートアイランド(神戸)
  • Year and Date: 2010-12-10
• [Presentation] 高トリグリセリド血症発症の病因としてのリポ蛋白リパーゼ(LPL)に対する自己抗体産生 (2010)
  • Author(s): 高木敦子、池田康行、荒木まり子、森田拓、石原正行、松本学、高杉尚志、前田明彦、阿部孝典、藤枝幹也、脇口宏
  • Organizer: 第83回 日本生化学会大会&第33回 日本分子生物学会大会(合同大会)
  • Place of Presentation: 神戸ポートアイランド(神戸)
  • Year and Date: 2010-12-10
• [Presentation] Environmental risk factors leading to hypertriglyceridemia on heterozygous lipoprotein lipase(LPL) deficiency identified in the general population of Japanese (2010)
  • Author(s): Y. Ikeda, A. Takagi, N. Iwai, Y. Kokubo, and H. Tomoike
  • Organizer: 78^<th> European Atheroclerosism Society Congress
  • Place of Presentation: Hamburg(GERMANY)
  • Year and Date: 2010-06-23
• [Presentation] Identification of compound heterozygous deficiency with a novel large deletion(a 54-kb deletion of 5' upper mregion and a part of intron 1) and y61x of the lipoprotein lipase gene in the Japanese subject (2010)
  • Author(s): A. Takagi, M. Nagano, T. Iwanaga, N. Ito, H. Hattori, T. Egashira, Y. Ikeda
  • Organizer: 78^<th> European Atheroclerosis Society Congress
  • Place of Presentation: Hamburg(GERMANY)
  • Year and Date: 2010-06-23
• [Presentation] Identification of compound heterozygous deficiency with a novel large deletion (a 54-kb deletion of 5' upper region and a part of intron 1) and y61x of the lipoprotein lipase gene in the Japanese subject (2010)
  • Author(s): A.Takagi, M.Nagano, T.Iwanaga, N.Ito, H.Hattori, T.Egashira, Y.Ikeda.
  • Organizer: 78^<th> EAS
  • Place of Presentation: Hamburg(GERMANY)
  • Year and Date: 2010-06-23
• [Presentation] Environmental risk factors leading to hypertriglyceridemia on heterozygous lipoprotein lipase (LPL) deficiency identified in the general population of Japanese. (2010)
  • Author(s): Y.Ikeda, A.Takagi, N.Iwai, Y.Kokubo, H.Tomoike.
  • Organizer: 78^<th> EAS
  • Place of Presentation: Hamburg (GERMANY)
  • Year and Date: 2010-06-23
• [Presentation] 日本人一般集団におけるリポ蛋白リパーゼ(LPL)遺伝子変異(第3報) S447X変異の頻度と諸性質:吹田研究 (2009)
  • Author(s): 高木敦子、池田康行、岩井直温、小久保喜弘、友池仁暢
  • Organizer: 第82回日本生化学会大会
  • Place of Presentation: 神戸国際会議場(兵庫県)
  • Year and Date: 2009-10-24
• [Presentation] 日本人一般集団におけるリポ蛋白リパーゼ(LPL)遺伝子変異(第3報)S447X変異の頻度と諸性質:吹田研究 (2009)
  • Author(s): 高木敦子、池田康行、岩井直温、小久保喜弘、友池仁暢
  • Organizer: 第82回 日本生化学会大会
  • Place of Presentation: 神戸国際会議場(兵庫県)
  • Year and Date: 2009-10-24
• [Presentation] 高脂血症を合併したSLEの1例 (2009)
  • Author(s): 荒木まり子、森田拓、石原正行、松本学、高杉尚志、前田明彦、阿部孝典、高木敦子、池田康行、藤枝幹也、脇口宏
  • Organizer: 第44回日本小児腎臓病学会学術集会
  • Place of Presentation: 一橋記念講堂・学術総合センター(東京)
  • Year and Date: 2009-06-27
• [Presentation] 高脂血症を合併したSLEの1例 (2009)
  • Author(s): 荒木まり子、森田拓、石原正行、松本学、高杉尚志、前田明彦、阿部孝典、高木敦子、池田康行、藤枝幹也、脇口宏
  • Organizer: 第44回 日本小児腎臓病学会学術集会
  • Place of Presentation: 一橋記念講堂・学術総合センター(東京)
  • Year and Date: 2009-06-27