Elsevier

Biological Psychiatry

Volume 59, Issue 7, 1 April 2006, Pages 652-659
Biological Psychiatry

Original article
Association Between Polymorphisms in the Promoter Region of the Sialyltransferase 8B (SIAT8B) Gene and Schizophrenia

https://doi.org/10.1016/j.biopsych.2005.08.016Get rights and content

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.

Section snippets

Subjects

For the case-control study, we recruited 188 unrelated schizophrenics, of whom 98 were male (mean age 54.2 ± 7.9) and 90 female (mean age 54.8 ± 12.7). All patients were diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) (American Psychiatric Association 1994), to give best-estimate lifetime diagnosis, with consensus from at least two experienced psychiatrists. All available medical records and family informant reports were also taken into

Detection of the SIAT8B and SIAT8D Gene Polymorphisms

The genomic layout of the human SIAT8B and SIAT8D genes, which span 70.3 kb on 15q26 and 96.1 kb on 5q21, respectively, are shown in Figure 1. The transcription start sites of both genes have been confirmed experimentally (Scheidegger et al 1995; http://dbtss.hgc.jp/). The SIAT8B gene is composed from 6 exons, and SIAT8D of 5 exons. Based on this structural information, we performed mutation screening of the genes, inspecting all exons, splice boundaries and the 5′ upstream region using 20

Discussion

While both SIAT8B and SIAT8D regulate the annexation of negatively charged oligosaccharides onto PSA, this study suggests that only SIAT8B may play a role in conferring susceptibility to Japanese schizophrenia. Despite the fact that polysaccharides are abundantly expressed in the brain and their crucial role in development and synaptic plasticity in the central nervous system, there have been no investigations of association between polysaccharide-synthesizing genes and schizophrenia. To our

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