Establishment of genetic diagnostics, preventive and development of treatment for atherogenic hypertriglyceridemia
| Project/Area Number |
16300228
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Applied health science
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| Research Institution | NATIONAL CARDIOVASCULAR CENTER RESEARCH INSTITUTE |
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Principal Investigator |
IKEDA Yasuyuki National Cardiovascular Center Research Institute, Etiology and Pathogenesis, Laboratory chief, 病因部, 室長 (90176107)
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| Co-Investigator(Kenkyū-buntansha) |
TAKAGI Atsuko National Cardiovascular Center Research Institute, Pharmacology, Laboratory chief, 薬理部, 室長 (90179416)
TAMASAWA Naoki Hirosaki University, School of Medicine Third Department of Internal Medicine, Associate Professor, 医学部第三内科, 助教授 (00236738)
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| Project Period (FY) |
2004 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥14,700,000 (Direct Cost: ¥14,700,000)
Fiscal Year 2006: ¥5,000,000 (Direct Cost: ¥5,000,000)
Fiscal Year 2005: ¥5,000,000 (Direct Cost: ¥5,000,000)
Fiscal Year 2004: ¥4,700,000 (Direct Cost: ¥4,700,000)
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| Keywords | Lipoprotein lipase / Hypertriglyceridemia / Lifestyle-related disease / Heterozygote / Electrochemical array chip / Protease-resistant / Nourishment guidance / Therapeutic exercise |
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| Research Abstract |
We summarize results obtained from the research program of 3 years through 2004 to 2006.
(1) Improvement of detection system using electrochemical array (ECA) chip for lipoprotein lipase (LPL) gene mutation and its application to clinical samples (Ikeda) : We developed a new simultaneous multiple mutation detection (SMMD) system using an ECA chip and ferrocenylnapthalene diimide, as the indicator (Ref.# 3 and 4). This SMMD system can simultaneously identify several genetic mutations such as single nucleotide polymorphism, insertion, deletion, translocation and short tandem repeat. By using the SMMD system, we newly identified two LPL gene mutations from subjects with hypertriglyceridemia.
(2) Treatment for hypertriglyceridemia developed in subjects with heterozygous LPL gene mutation by improving their lifestyle to a healthful one (Tamasawa and Ikeda) : Subjects (carriers) with heterozygous LPL deficiency are prone to develop mild hypertriglyceridemia (type IV hyperlipoproteinemia) when
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complicated with environmental factors such as a hyperinsulinemic state and/or a high alcohol intake, which stimulate triglyceride synthesis in the liver, while carriers are normolipidemic provided that they do not have the environmental factors (Ref.# 2). Our research revealed that hypertriglyceridemia in the carriers became normolipidemic state by getting the carriers to change to a more healthful lifestyle.
(3) Development of a protease-resistant LPL molecule based on LPL gene information and its application to treatment (Takagi and Ikeda) : Because a native LPL molecule was inactivated by proteases in bloodstream, the protease-resistant LPL molecule was constructed by exchanging a target amino acid to a glycine. The protease-resistant LPL molecule exhibited 30% of the triglyceride hydrolyzing function in comparison to that of the native LPL molecule. Since it was clarified that this protease-resistant LPL molecule was steady for at least six hours at 37℃ after the protease-resistant LPL molecule was mixed with human blood, the possibility that the protease-resistant LPL molecule was able to be used as a hypertriglyceridemic treatment was confirmed. To judge the treatment effect of the protease-resistant LPL molecule to hypertriglyceridemia, it was necessary to detect a molecular characteristic of hepatic triglyceride lipase (HTGL). Therefore, ELISA system for the determination of HTGL mass was established (Ref.# 1). Less
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Report
(4 results)
Research Products
(20 results)
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[Journal Article] Genotyping of the human lipoprotein lipase gene by ferrocenylnaphthalene diimide-based electrochemical hybridization assay2005
Author(s)
Nojima, T, Yamashita, K, Takagi, A, Ikeda, Y, Kondo, H, Takenaka, S.
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Journal Title
Analytical Sciences 21(12)
Pages: 1437-1441
NAID
Related Report
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[Journal Article] Glucose-stimulated insulin response in non-diabetic patients with lipoprotein lipase deficiency and hypertriglyceridemia2005
Author(s)
Tamasawa, N, Matsui, J, Murakami, H, Tanabe, J, Matsuki, K, Ogawa, Y, Ikeda, Y, Takagi, A, Suda
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Journal Title
Diabetes Research and Clinical Practice
Related Report
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