2007 Fiscal Year Final Research Report Summary
Study on the mechanism of rhabdomyosis induced by statins and gene analysis of patients with rhalxiomyasis
| Project/Area Number |
18590525
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Laboratory medicine
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| Research Institution | Gifu University |
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Principal Investigator |
TAKEMURA Masao Gifu University, Graduate School of Medicine, Assistant Professor (80402155)
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| Co-Investigator(Kenkyū-buntansha) |
SEISHIMA Mitsuru Gifu University, Graduate School of Medicine, Professor (10171315)
SAITO Kuniaki Gifu University, Graduate School of Medicine, Part-time Lecturer (80262765)
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| Project Period (FY) |
2006 – 2007
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| Keywords | hyperlipidemia / statin drugs / rhabdomvosis |
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| Research Abstract |
TO investigate the mechanism of rhabdomyosis induced by statin drugs, we confirmed the expression of Ryanodine receptor type 1 (RyR1), which is a responsible gene for malignant hyperthermia, in human peripheral blood mononuclear cells (PBMC). We also determined the increment of calcium concentration in PBMC when various statins were added. Rosuvastatin, Simvastatin, Fluvastatin and Cerivastatin increased CO- in PBMC, but Pravastatin did not Since Rosuvastatin increased Ca2+ most, we used Rosuvastatin in further in vitro study Rosuvastatin was added on PBMC in patients treated with statins The increment of Cats- in PMBC was significantly increased in 15 patients with high serum CK level compared to 5 patients with normal CK level. (P<0.0001), but there was no difference in Ca^(2+) increment between 45 healthy controls and 5 patients with normal CK The increment of Cd^(2+) in PMBC by the addition of statins is considered to be derived from SKR and mitochondria. In addition, we investigated the effect of Xestospongin C, an thibitor of 1P3 receptor, but we could not determine the origin of Ca^(2+) release, IP3 receptor or RyR. We analyzed genotype of RyR in patients with high CK, but we could not find any RyR mutations.
In conclusion, it is useful to determine Ca^(2+) concentration in PBMC stimulated by statins for the elimination of side effect such as rhabdomyosis caused by statins.
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