Association between polymorphisms in the promoter region of the sialyltransferase 8B (SIAT8B) gene and schizophrenia.
BACKGROUND
Sialyltransferase 8B (SIAT8B) and 8D (SIAT8D) are two polysialyltransferases that catalyze the transfer of polysialic acid (PSA) to the neural cell adhesion molecule 1 (NCAM1). PSA modification of NCAM1 plays an important role in neurodevelopment of the brain and disruption of this process is postulated as an etiologic factor in psychiatric disorders. Altered levels of the PSA-NCAM1 in the brain of schizophrenics have been reported, suggesting a role for this molecule in the disorder.


METHODS
We performed an association study of single nucleotide polymorphisms (SNPs) within SIAT8B and SIAT8D, using 188 schizophrenics and 156 age and gender matched controls. All genotypes were determined by polymerase chain reaction (PCR) amplification and direct sequencing.


RESULTS
Two polymorphisms, -1126T > C and -851T > C, located in the promoter region of SIAT8B showed nominally significant association with schizophrenia (allelic associations, p = .014 and p = .007, respectively), and haplotypes constructed from three additional SNPs located in the same linkage disequilibrium block were associated with schizophrenia. Furthermore an in vitro promoter assay revealed that a reporter construct containing a risk haplotype for SIAT8B had significantly higher transcriptional activity compared with one containing a protective haplotype (p = .021). In contrast, no significant association was observed between any variations in SIAT8D and schizophrenia.


CONCLUSIONS
The present study suggests that functional promoter SNPs of SIAT8B could confer a risk for schizophrenia in the Japanese population.
Arai
Makoto
M
Department of Schizophrenia Research, Tokyo Institute of Psychiatry, Tokyo, Japan.
Yamada
Kazuo
K
Toyota
Tomoko
T
Obata
Nanako
N
Haga
Seiichi
S
Yoshida
Yuuki
Y
Nakamura
Kazuhiko
K
Minabe
Yoshio
Y
Ujike
Hiroshi
H
Sora
Ichiro
I
Ikeda
Kazuhiko
K
Mori
Norio
N
Yoshikawa
Takeo
T
Itokawa
Masanari
M
D000483:Alleles; D044466:Asian People; D001483:Base Sequence / Q000235:genetics; D001921:Brain / Q000378:metabolism*; D020134:Catalytic Domain / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D005260:Female; D017353:Gene Deletion; D005838:Genotype; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D019006:Neural Cell Adhesion Molecules / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012559:Schizophrenia / Q000208:ethnology / Q000235:genetics / Q000378:metabolism; D012794:Sialic Acids / Q000378:metabolism; D012799:Sialyltransferases / Q000235:genetics*
D017931:DNA Primers; D019006:Neural Cell Adhesion Molecules; D012794:Sialic Acids; C021319:polysialic acid; C046778:CMP-N-acetylneuraminate-poly-alpha-2,8-sialosyl sialyltransferase; D012799:Sialyltransferases