Failure to confirm genetic association of the FXYD6 gene with schizophrenia: the Japanese population and meta-analysis.
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.
Iwata
Yasuhide
Y
Department of Psychiatry and Neurology, Hamamatsu University School of Medicine, Shizuoka, Japan.
Yamada
Kazuo
K
Iwayama
Yoshimi
Y
Anitha
Ayyappan
A
Thanseem
Ismail
I
Toyota
Tomoko
T
Hattori
Eiji
E
Ohnishi
Tetsuo
T
Maekawa
Motoko
M
Nakamura
Kazuhiko
K
Suzuki
Katsuaki
K
Matsuzaki
Hideo
H
Tsuchiya
Kenji J
KJ
Suda
Shiro
S
Sugihara
Genichi
G
Takebayashi
Kiyokazu
K
Yamamoto
Shigeyuki
S
Iwata
Keiko
K
Mori
Norio
N
Yoshikawa
Takeo
T
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
C531119:FXYD6 protein, human; D007473:Ion Channels; D000254:Sodium-Potassium-Exchanging ATPase