Genetic and functional analyses of the gene encoding synaptophysin in schizophrenia

Yu Chih Shen, Ho Min Tsai, Jhen Wei Ruan, Yi Chu Liao, Shih Fen Chen, Chia Hsiang Chen*

*此作品的通信作者

研究成果: 期刊稿件文章同行評審

14 引文 斯高帕斯(Scopus)

摘要

Objectives: 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. Conclusion: 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.

原文英語
頁(從 - 到)14-19
頁數6
期刊Schizophrenia Research
137
發行號1-3
DOIs
出版狀態已出版 - 05 2012
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