title: Association between polymorphisms in the promoter region of the sialyltransferase 8B (SIAT8B) gene and schizophrenia.
abstract: 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.
authors.affiliation: Department of Schizophrenia Research, Tokyo Institute of Psychiatry, Tokyo, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Arai
authors.forename: Kazuo
authors.initials: K
authors.lastname: Yamada
authors.forename: Tomoko
authors.initials: T
authors.lastname: Toyota
authors.forename: Nanako
authors.initials: N
authors.lastname: Obata
authors.forename: Seiichi
authors.initials: S
authors.lastname: Haga
authors.forename: Yuuki
authors.initials: Y
authors.lastname: Yoshida
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakamura
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Minabe
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ujike
authors.forename: Ichiro
authors.initials: I
authors.lastname: Sora
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Ikeda
authors.forename: Norio
authors.initials: N
authors.lastname: Mori
authors.forename: Takeo
authors.initials: T
authors.lastname: Yoshikawa
authors.forename: Masanari
authors.initials: M
authors.lastname: Itokawa
mesh_terms: 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*
chemical_list: 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