Department of Psychiatry and Neurology, Hamamatsu University School of Medicine, Shizuoka, Japan.
Am J Med Genet B Neuropsychiatr Genet. 2010 Sep;153B(6):1221-7. doi: 10.1002/ajmg.b.31095.
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.
FXYD 结构域包含的离子转运调节剂 6（FXYD6）基因编码磷酸酯酶，通过改变 Na，K-ATP 酶的动力学特性来调节细胞离子转运。磷酸酯酶在与精神分裂症相关的大脑区域中高度表达。FXYD6 基因位于 11q22-24 染色体上，这是精神分裂症最确定的连锁区域之一。因此，FXYD6 中的遗传变异，包括调节基因组元件，可能导致磷酸酯酶的异常功能或表达，并增加精神分裂症的遗传风险。先前的研究表明，FXYD6 中的多态性与英国样本中的精神分裂症有关。然而，在日本人群中报道了相互矛盾的结果。在这项研究中，我们旨在使用来自同种基因日本人群（1060 名精神分裂症患者和 1060 名年龄和性别匹配的对照者）的不同样本检验先前的遗传关联发现。从 FXYD6 基因中，我们检查了六个单核苷酸多态性（rs11216573、rs555577、rs1815774、rs4938445、rs4938446 和 rs497768），这些多态性以前都被分析过与关联。我们没有在我们的日本样本中检测到任何显著的等位基因、基因型或单倍型关联。纳入先前和本研究的荟萃分析也表明，FXYD6 基因与精神分裂症无关。我们的结论是，FXYD6 基因在不同人群中对精神分裂症的易感性没有主要影响。
