2005 Fiscal Year Final Research Report Summary
Genetic determination and pathogenesis in thyrotoxic periodic paralysis
| Project/Area Number |
16590836
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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 |
Neurology
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| Research Institution | Kagoshima University |
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Principal Investigator |
ARIMURA Kimiyoshi Kagoshima University, Graduate School of Medical and Dental Sciences, Associate Professor, 大学院・医歯学総合研究科, 助教授 (20159510)
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| Co-Investigator(Kenkyū-buntansha) |
TAKASHIMA Hiroshi Kagoshima University, Graduate School of Medical and Dental Sciences, Research Associate, 大学院・医歯学総合研究科, 助手 (80372803)
KAMEYAMA Masaki Kagoshima University, Graduate School of Medical and Dental Sciences, Professor, 大学院・医歯学総合研究科, 教授 (60150059)
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| Project Period (FY) |
2004 – 2005
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| Keywords | thyrotoxic periodic paralysis / prolonged exercise test / muscle ion channel / voltage-gated potassium channel / polymorphism |
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| Research Abstract |
Thyrotoxic periodic paralysis (TPP) is a well known complication of thyrotoxicosis especially in Asian male. The incidence is 1.9% in Japan and 1.8% in China. TPP is seen in 8% of thyrotoxic patients. The diagnosis of TPP is made by the periodic paralysis provoked by heavy meals and exercise, low serum K level and hyperthyroidism. Prolonged exercise test (PET) is positive in most of TPP patients. The pathogenesis of TPP is speculated to be due to the massive shift of potassium into muscle from extra-cellular compartment by hyperactivity of Na/K ATPase pump activity. PET results as well as in vitro microelectrode study in muscle fibers obtained from TPP patients suggest that the pre-existing membrane excitability may be another cause of TPP.
We hypothesize that genetic abnormality of muscle channel ion channel genes may cause in TPP. To date, 4 ion channel genes expressed in skeletal muscle, i.e. CACNA1S, SCN4A, KCNJ2 and KCNE3 have been studied. In this study, we assumed the voltage-gated potassium channel, α-subunit Kv7.5 encoded by KCNQ5 gene to be a candidate gene for TPP, since K+ conductance of patients' muscle was decreased using in vitro microelectrode studies. We analyzed KCNQ5 gene, in addition to the previously examined ion channels, KCNJ2, KCNE3, CACNA1S and SCN4A, in 7 Japanese TPP patients confirmed by the characteristic clinical features and positive PET. DNA analysis showed 5 synonymous SNPs in KCNQ5, KCNJ2, KCNE3 and CACNA1S genes. We could not find a causative variant in the KCNQ5 gene, however, we could not explain the meaning of synonymous SNPs for susceptibility to TPP. Further study such as international collaboration will be needed to have a conclusion of the meaning of synonymous SNPs of ion channel genes.
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