Association between polymorphisms in the promoter region of the sialyltransferase 8B (SIAT8B) gene and schizophrenia
Association between polymorphisms in the promoter region of the sialyltransferase 8B (SIAT8B) gene and schizophrenia
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DOI：
10.1016/j.biopsych.2005.08.016
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发表时间：
2006-04-01
影响因子：
10.6
通讯作者：
Itokawa, M
中科院分区：
文献类型：
--
作者：
Arai, M;Yamada, K;Itokawa, M
背景资料：唾液酸转移酶8B（SIAT 8B）和8D（SIAT 8D）是两种多聚唾液酸转移酶，催化多聚唾液酸（PSA）转移到神经细胞粘附分子1（NCAM 1）。NCAM 1的PSA修饰在脑的神经发育中起重要作用，并且该过程的破坏被假定为精神疾病的病因学因素。改变水平的PSA-NCAM 1在大脑中的精神分裂症已被报道，这表明该分子在disorder.Methods的作用：我们进行了关联研究的单核苷酸多态性（SNP）内SIAT 8B和SIAT 8D，使用188精神分裂症和156年龄和性别匹配的对照。所有的基因型通过聚合酶链反应（PCR）扩增，直接测序确定。结果：两个多态性，-1126 T>C和-851 T>C，位于启动子区的SIAT 8B显示名义上显着关联与精神分裂症（等位基因协会，p= 0.14和p= 0.007，分别），和单倍型构建从？位于同一连锁不平衡区的另外三个SNPs与精神分裂症相关。此外，体外启动子测定显示，与含有保护性单倍型的报道构建体相比，含有SIAT 8B风险单倍型的报道构建体具有显著更高的转录活性（p= 0.021）。相比之下，没有显着的关联之间的任何变化，SIAT 8D和schizophrenia.Conclusions：本研究表明，功能启动子单核苷酸多态性SIAT 8B可以赋予精神分裂症的风险在日本人口。
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=.0.14 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.