| Project/Area Number |
17591789
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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 |
Otorhinolaryngology
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| Research Institution | Osaka University |
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Principal Investigator |
DOI Katsumi Osaka University, Graduate School of Medicine, Associate Professor (40243224)
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| Co-Investigator(Kenkyū-buntansha) |
KITAHARA Tadashi Osaka University, Graduate School of Medicine, Assistant (30343255)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2006: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2005: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | Meniere's disease / endolymphatic hydrops / KCNE potassium channel / SNP / genetic factor / 遺伝子解析 / KCNE1 / KCNE3 |
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| Research Abstract |
The present study confirmed the expression of KCNE1 potassium channel in the cochlea and that of KCNE3 potassium channel in the endolymphatic sac. KCNE1 and KCNE3 potassium channels may be active and play an essential role in trans-membrane ion and water transport in the inner ear. Because IH and ISH studies demonstrated that KCNE1 channel was mainly expressed in the marginal cells of the stria vascularis while KCNE3 potassium channel was intensely expressed in the epithelium of distal portion of the endolymphatic sac.
The SNP analyses confirmed 112G/A SNP in KCNE1 potassium channel gene and 198T/C SNP in KCNE3 potassium channel gene in both MD patients and non-MD control subjects. Significant difference in prevalence of each SNP in both genes was confirmed between MD and non-MD control subjects: High prevalence of 112A homozygote or 112G/A heterozygote (112A on one or both allele) in KCNE1 gene and high prevalence of 198C homozygote or 198T/C heterozygote (198C on one or both allele) was detected in MD patients. The result indicates that 112G/A SNP in KCNE1 gene and 198T/C SNP in KCNE3 gene should determine an increased susceptibility to develop MD.
The etiology of MD is likely to be multi-factorial, with one of the factors being a genetic predisposition. Recent studies suggest that the COCH gene, HLA class I and II antigens, and Antiquitin might be one of the genetic factors contributing to familiar and sporadic MD. 6-8 A candidate gene analysis to approach the genetic basis of MD has just initiated now and the future study should identify novel mutations/polymorphisms in several candidate genes for both the sporadic and inherited forms of MD. The present study first succeeds to identify both KCNE1 and KCNE3 potassium channel genes as the candidate genes for the sporadic forms of MD.
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