title: Failure to confirm genetic association of the FXYD6 gene with schizophrenia: the Japanese population and meta-analysis.
abstract: 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.
authors.affiliation: Department of Psychiatry and Neurology, Hamamatsu University School of Medicine, Shizuoka, Japan.
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Iwata
authors.forename: Kazuo
authors.initials: K
authors.lastname: Yamada
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Iwayama
authors.forename: Ayyappan
authors.initials: A
authors.lastname: Anitha
authors.forename: Ismail
authors.initials: I
authors.lastname: Thanseem
authors.forename: Tomoko
authors.initials: T
authors.lastname: Toyota
authors.forename: Eiji
authors.initials: E
authors.lastname: Hattori
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Ohnishi
authors.forename: Motoko
authors.initials: M
authors.lastname: Maekawa
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakamura
authors.forename: Katsuaki
authors.initials: K
authors.lastname: Suzuki
authors.forename: Hideo
authors.initials: H
authors.lastname: Matsuzaki
authors.forename: Kenji J
authors.initials: KJ
authors.lastname: Tsuchiya
authors.forename: Shiro
authors.initials: S
authors.lastname: Suda
authors.forename: Genichi
authors.initials: G
authors.lastname: Sugihara
authors.forename: Kiyokazu
authors.initials: K
authors.lastname: Takebayashi
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Yamamoto
authors.forename: Keiko
authors.initials: K
authors.lastname: Iwata
authors.forename: Norio
authors.initials: N
authors.lastname: Mori
authors.forename: Takeo
authors.initials: T
authors.lastname: Yoshikawa
mesh_terms: D000328:Adult; D000483:Alleles; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D007473:Ion Channels / Q000235:genetics*; D007564:Japan; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012559:Schizophrenia / Q000208:ethnology / Q000235:genetics*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
chemical_list: C531119:FXYD6 protein, human; D007473:Ion Channels; D000254:Sodium-Potassium-Exchanging ATPase