Molecular Otolaryngology Research Laboratories, Department of Otolaryngology - Head and Neck Surgery, University of Iowa, Iowa City, IA 52242, USA.
Am J Med Genet A. 2010 Jan;152A(1):67-74. doi: 10.1002/ajmg.a.33114.
Ménière disease (MD) is a complex disorder of unknown etiology characterized by the symptom triad of vertigo, sensorineural hearing loss, and tinnitus. Its reported incidence is 1-2 per 1,000 in Caucasians and 0.03-0.37 per 1,000 in Japanese. Doi et al. [Doi et al. (2005); ORL J Otorhinolaryngol Relat Spec 67:289-293] recently reported that two single nucleotide polymorphisms (SNPs) in KCNE1 and KCNE3 are associated with MD in Japanese subjects. Consistent with this possibility, these two genes encode potassium channels that are expressed in the stria vascularis and endolymphatic sac, respectively, and their role in ion transport suggests that they may be important in inner ear homeostasis. To establish whether a similar association exists in the Caucasian MD population, we sequenced the coding regions and exon-intron boundaries of both genes in 180 Caucasian persons with MD and 180 matched Caucasian controls. Neither of the two reported SNPs was significantly associated with MD when compared to the Caucasian controls (KCNE1, P = 0.55; KCNE3, P = 0.870). Comparison of allele frequencies between the Japanese MD population and our study population revealed no significant difference between groups (KCNE1, P = 0.90; KCNE3, P = 0.862), suggesting that the significant differences reported in the Japanese study arose from their control population. Six additional SNPs in both KCNE1 and KCNE3 were genotyped and none was associated with MD. Population stratification within our MD and Caucasian control population was excluded. Our data show that SNPs in KCNE1 and KCNE3 are not associated with MD in Caucasians.
梅尼埃病（MD）是一种病因不明的复杂疾病，其特征为眩晕、感音神经性听力损失和耳鸣三联征。在白种人群中的发病率为 1-2/1000，在日本人群中的发病率为 0.03-0.37/1000。Doi 等人[Doi 等人（2005）；ORL J Otorhinolaryngol Relat Spec 67:289-293]最近报道，KCNE1 和 KCNE3 中的两个单核苷酸多态性（SNP）与日本 MD 患者相关。这两种基因分别编码在血管纹和内淋巴囊中表达的钾通道，与这一发现一致，它们在离子转运中的作用表明它们可能对内耳内环境稳定具有重要作用。为了确定这种相关性是否存在于白种人 MD 人群中，我们对 180 名白种人 MD 患者和 180 名匹配的白种人对照者的 KCNE1 和 KCNE3 基因的编码区和外显子-内含子边界进行了测序。与白种人对照组相比，这两个报道的 SNP 均与 MD 无显著相关性（KCNE1，P=0.55；KCNE3，P=0.870）。与日本 MD 人群相比，我们研究人群中的等位基因频率无显著差异（KCNE1，P=0.90；KCNE3，P=0.862），这表明日本研究中报道的显著差异源于他们的对照组人群。对 KCNE1 和 KCNE3 中的另外 6 个 SNP 进行了基因分型，结果均与 MD 无关。排除了我们的 MD 患者和白种人对照组人群中的群体分层。我们的数据表明，KCNE1 和 KCNE3 中的 SNP 与白种人 MD 无关。
