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

本研究证实KCNE1钾通道在耳蜗处表达，KCNE3钾通道在内淋巴囊中表达。KCNE1和KCNE3钾通道可能是激活的，在内耳跨膜离子和水的运输中起重要作用。由于IH和ISH研究表明KCNE1通道主要表达于血管纹边缘细胞，而KCNE3钾通道主要表达于内淋巴囊远端上皮细胞。SNP分析证实MD患者和非MD对照组KCNE1钾通道基因存在112G/A SNP，KCNE3钾通道基因存在198T/C SNP。在MD和非MD对照组中，两个基因的每个SNP的患病率均有显著差异：MD患者KCNE1基因112A纯合子或112G/A杂合子(一个或两个等位基因均为112A)和198C纯合子或198T/C杂合子(一个或两个等位基因均为198C)的患病率较高。结果表明，KCNE1基因的112G/A单核苷酸多态和KCNE3基因的198T/C单核苷酸多态可能增加了MD的易感性。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、HLAI、II类抗原和安替奎因可能是家族性和散发性MD的遗传因素之一。6-8探讨MD遗传基础的候选基因分析现在刚刚开始，未来的研究应该发现散发性和遗传性MD的几个候选基因中的新突变/多态。本研究首次成功地将KCNE1和KCNE3钾通道基因确定为散发性MD的候选基因。

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.