权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Characterization of KCNE/KCNQ potassium channels in the rat inner ear.

大鼠内耳 KCNE/KCNQ 钾通道的表征。

基本信息

批准号：
17591789
负责人：
DOI Katsumi
金额：
$ 2.18万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17591789/
关键词：
Meniere's disease endolymphatic hydrops KCNE potassium channel SNP genetic factor 遺伝子解析 KCNE1 KCNE3

项目摘要

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.

本研究证实KCNE1钾通道在耳蜗中表达，KCNE3钾通道在内淋巴囊中表达。KCNE1和KCNE3钾通道可能是活跃的，在内耳跨膜离子和水分运输中起重要作用。因为IH和ISH研究表明KCNE1通道主要表达于血管纹边缘细胞，而KCNE3钾通道则强烈表达于内淋巴囊远端上皮。SNP分析证实，在MD患者和非MD对照组中，KCNE1钾通道基因为112G/A SNP， KCNE3钾通道基因为198T/C SNP。在MD和非MD对照组中，两种基因各SNP的患病率均存在显著差异：KCNE1基因112A纯合子或112G/A杂合子（112A在一个或两个等位基因上）的患病率较高，MD患者中检测到198C纯合子或198T/C杂合子（198C在一个或两个等位基因上）的患病率较高。结果表明，KCNE1基因112G/A SNP和KCNE3基因198T/C SNP可能决定了MD易感性的增加。MD的病因可能是多因素的，其中一个因素是遗传易感性。最近的研究表明，COCH基因，HLA I类和II类抗原，和Antiquitin可能是导致常见和散发性MD的遗传因素之一。6-8对MD的遗传基础的候选基因分析刚刚开始，未来的研究应该在散发性和遗传性MD的候选基因中发现新的突变/多态性。本研究首次成功地确定了KCNE1和KCNE3钾通道基因作为散发性MD的候选基因。