Association of SOX10 with schizophrenia in the Japanese population.
BACKGROUND
Microarray studies of schizophrenic brains revealed decreases in the expression of myelin and oligodendrocyte-related genes. Of these genes, sex-determining region Y-box 10 (SOX10) is a major transcription factor modulating the expression of proteins involved in neurogenesis and myelination. The SOX10 gene is located on chromosome 22q13.1, a region repeatedly reported to show positive signals in linkage studies on schizophrenia.


OBJECTIVE
This study was conducted to clarify the exact role of SOX10 in the pathophysiology of schizophrenia.


METHODS
We performed an association analysis of SOX10 in a Japanese population of 915 schizophrenic patients and 927 controls. Genotyping was carried out using polymerase chain reaction restriction fragment length polymorphism.


RESULTS
One single nucleotide polymorphism of the SOX10 gene (rs139,887) was selected as a haplotype tag single nucleotide polymorphism using 96 controls. A significant association was observed in the genotype and allelic frequency of this single nucleotide polymorphism between schizophrenic patients and controls (P=0.025 and P=0.009, respectively). Especially, a significant association was found in male patients, but not female patients. We also performed a mutational search of the whole coding region, branch site, and promoter region of SOX10 in 96 schizophrenic patients, but no potential functional polymorphisms were detected.


CONCLUSIONS
This study suggests that the SOX10 gene is related to the development of schizophrenia in the Japanese population.
Maeno
Nobuhisa
N
Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Takahashi
Nagahide
N
Saito
Shinichi
S
Ji
Xiaofei
X
Ishihara
Ryoko
R
Aoyama
Nagisa
N
Branko
Aleksic
A
Miura
Hideki
H
Ikeda
Masashi
M
Suzuki
Tatsuyo
T
Kitajima
Tsuyoshi
T
Yamanouchi
Yoshio
Y
Kinoshita
Yoko
Y
Iwata
Nakao
N
Inada
Toshiya
T
Ozaki
Norio
N
D000328:Adult; D000368:Aged; D002874:Chromosome Mapping; D002892:Chromosomes, Human, Pair 22; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006609:High Mobility Group Proteins / Q000235:genetics*; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D012016:Reference Values; D055757:SOXE Transcription Factors; D012559:Schizophrenia / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*
D017931:DNA Primers; D004268:DNA-Binding Proteins; D006609:High Mobility Group Proteins; C527923:SOX10 protein, human; D055757:SOXE Transcription Factors; D014157:Transcription Factors