title: A genetic association study of the FXYD domain containing ion transport regulator 6 (FXYD6) gene, encoding phosphohippolin, in susceptibility to schizophrenia in a Japanese population.
abstract: The FXYD domain containing ion transport regulator 6 (FXYD6) gene is located within a region of chromosome 11 (11q23.3) that has been shown by a number of genome scans to be one of the most well-established linkages to schizophrenia. FXYD6 encodes the protein phosphohippolin, which is primarily expressed in the brain. Phosphohippolin modulates the kinetic activity of Na,K-ATPase and has long-term physiological importance in maintaining cation homeostasis. A recent study reported that FXYD6 was associated with schizophrenia in the United Kingdom samples. Applying the gene-based association concept, we carried out an association study regarding FXYD6 and schizophrenia in a Japanese population, with a sample consisting of 2026 subjects (906 schizophrenics and 1120 controls). After linkage disequilibrium analysis, 23 single nucleotide polymorphisms (SNPs) were genotyped using 5'-exonuclease allelic discrimination assay. We found a significant association of two SNPs (rs11216573; genotypic P value: 0.022 and rs555577; genotypic P value: 0.026, allelic P value: 0.011, uncorrected). Nominal P values did not survive correction for multiple testing (rs11216573; genotypic P value: 0.47 and rs555577; genotypic P value: 0.55, allelic P value: 0.24, after SNPSpD correction). No association was observed between schizophrenia patients and controls in allelic, genotypic and haplotypic analyses. Our findings suggest that FXYD6 is unlikely to be related to the development of schizophrenia in a Japanese population.
authors.affiliation: Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan. y-ito@med.nagoya-u.ac.jp
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Ito
authors.forename: Yukako
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Nagahide
authors.initials: N
authors.lastname: Takahashi
authors.forename: Shinichi
authors.initials: S
authors.lastname: Saito
authors.forename: Branko
authors.initials: B
authors.lastname: Aleksic
authors.forename: Nakao
authors.initials: N
authors.lastname: Iwata
authors.forename: Toshiya
authors.initials: T
authors.lastname: Inada
authors.forename: Norio
authors.initials: N
authors.lastname: Ozaki
mesh_terms: D000328:Adult; D000368:Aged; D001921:Brain / Q000378:metabolism* / Q000503:physiopathology; D001923:Brain Chemistry / Q000235:genetics*; D002412:Cations / Q000378:metabolism; D002874:Chromosome Mapping; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D007473:Ion Channels / Q000737:chemistry / Q000235:genetics*; D007564:Japan / Q000208:ethnology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D017434:Protein Structure, Tertiary / Q000235:genetics; D012559:Schizophrenia / Q000208:ethnology / Q000235:genetics* / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
chemical_list: D002412:Cations; C531119:FXYD6 protein, human; D005819:Genetic Markers; D007473:Ion Channels; D000254:Sodium-Potassium-Exchanging ATPase