Failure to Confirm Genetic Association of the FXYD6 Gene With Schizophrenia: The Japanese Population and Meta-Analysis
Failure to Confirm Genetic Association of the FXYD6 Gene With Schizophrenia: The Japanese Population and Meta-Analysis
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DOI：
10.1002/ajmg.b.31095
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发表时间：
2010-09-01
影响因子：
2.8
通讯作者：
Yoshikawa, Takeo
中科院分区：
文献类型：
--
作者：
Iwata, Yasuhide;Yamada, Kazuo;Yoshikawa, Takeo
含有FXYD结构域的离子转运调节因子6（FXYD 6）基因编码磷酸化海马蛋白，其通过改变Na，K-ATP酶的动力学性质来调节细胞离子转运。磷酸化脑磷脂在与精神分裂症相关的大脑区域高度表达。FXYD 6基因位于染色体11 q22 -24，这是精神分裂症最常见的连锁区域之一。因此，FXYD 6中的遗传变异，包括调控基因组元件，可能会导致磷酸海马蛋白的功能或表达异常，并增加精神分裂症的遗传风险。之前的一项研究表明，FXYD 6的多态性与英国样本中的精神分裂症相关。然而，在日本人群中报告了相互矛盾的结果。在这项研究中，我们的目的是使用来自种族同质的日本人群（1，060名精神分裂症患者和1，060名年龄和性别匹配的对照）的不同样本来测试先前的遗传关联结果。从FXYD 6基因，我们检查了6个单核苷酸多态性（rs 11216573，rs 555577，rs 1815774，rs 4938445，rs 4938446和rs 497768），所有这些都是以前分析的关联。我们没有发现任何显着的等位基因，基因型或单倍型协会在我们的日本样本。荟萃分析结合以前和现在的研究也表明，FXYD 6基因与精神分裂症无关。我们的结论是，FXYD 6基因没有一个重大的影响，精神分裂症的易感性跨人群。(C)2010 Wiley-Liss，Inc.
The FXYD domain-containing ion transport regulator 6 (FXYD6) gene encodes phosphohippolin that regulates cellular ion transport by altering the kinetic properties of Na,K-ATPase. Phosphohippolin is highly expressed in brain regions that are relevant to schizophrenia. The FXYD6 gene is located at chromosome 11q22-24, one of the most established linkage regions for schizophrenia. Therefore, it may be possible that genetic variants in FXYD6, including the regulatory genomic elements could cause abnormal function or expression of phosphohippolin and increase the genetic risk for schizophrenia. A previous study suggested that polymorphisms in FXYD6 are associated with schizophrenia in UK samples. However, conflicting results have been reported in the Japanese population. In this study, we aimed to test the prior genetic association findings using different samples from the ethnically homogeneous Japanese population (1,060 schizophrenic patients and 1,060 age- and sex-matched controls). From the FXYD6 gene, we examined six single nucleotide polymorphisms (rs11216573, rs555577, rs1815774, rs4938445, rs4938446, and rs497768), all of which were previously analyzed for association. We did not detect any significant allelic, genotypic or haplotypic association in our Japanese samples. Meta-analysis incorporating previous and the present studies also showed that the FXYD6 gene is not associated with schizophrenia. We conclude that the FXYD6 gene does not have a major influence on susceptibility to schizophrenia across populations. (C) 2010 Wiley-Liss, Inc.