title: Genetic and functional analyses of the gene encoding synaptophysin in schizophrenia.
abstract: OBJECTIVE
  Synaptophysin (SYP) has been shown to be critical for regulating neurotransmitter release and synaptic plasticity, a process thought to be disrupted in schizophrenia. In addition, abnormal SYP expression in different brain regions has been linked to this disorder in postmortem brain studies. We investigated the involvement of the SYP gene in the susceptibility to schizophrenia.
  
  
  METHODS
  We searched for genetic variants in the promoter region, all exons, and both UTR ends of the SYP gene using direct sequencing in a sample of patients with schizophrenia (n=586) and non-psychotic controls (n=576), both being Han Chinese from Taiwan, and conducted an association and functional study.
  
  
  RESULTS
  We identified 2 common SNPs (c.*4+271A>G and c.*4+565T>C) in the SYP gene. SNP and haplotype-based analyses displayed no associations with schizophrenia. In addition, we identified 6 rare variants in 7 out of 586 patients, including 1 variant (g.-511T>C) located at the promoter region, 1 synonymous (A104A) and 2 missense variants (G293A and A324T) located at the exonic regions, and 2 variants (c.*31G>A and c.*1001G>T) located at the 3'UTR. No rare variants were found in the control subjects. The results of the reporter gene assay demonstrated the influence of g.-511T>C and c.*1001G>T on the regulatory function of the SYP gene, while that the influence of c.*31G>A may be tolerated. In silico analysis demonstrated the functional relevance of other rare variants.
  
  
  CONCLUSIONS
  Our study lends support to the hypothesis of multiple rare mutations in schizophrenia, and provides genetic clues that indicate the involvement of SYP in this disorder.
authors.affiliation: Department of Psychiatry, Tzu Chi General Hospital, Hualien, Taiwan.
authors.forename: Yu-Chih
authors.initials: YC
authors.lastname: Shen
authors.forename: Ho-Min
authors.initials: HM
authors.lastname: Tsai
authors.forename: Jhen-Wei
authors.initials: JW
authors.lastname: Ruan
authors.forename: Yi-Chu
authors.initials: YC
authors.lastname: Liao
authors.forename: Shih-Fen
authors.initials: SF
authors.lastname: Chen
authors.forename: Chia-Hsiang
authors.initials: CH
authors.lastname: Chen
mesh_terms: D000328:Adult; D045744:Cell Line, Tumor; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D009447:Neuroblastoma / Q000473:pathology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D012559:Schizophrenia / Q000235:genetics*; D016708:Synaptophysin / Q000235:genetics*; D013624:Taiwan; D014162:Transfection
chemical_list: D016708:Synaptophysin