Promoter variant rs2301228 on the neural cell adhesionmolecule 1 gene confers risk of schizophrenia in Han Chinese

CORC > 昆明动物研究所 > 昆明动物研究所 > 动物模型与人类重大疾病机理重点实验室 > 重大疾病机理的遗传学

	Promoter variant rs2301228 on the neural cell adhesionmolecule 1 gene confers risk of schizophrenia in Han Chinese
	Zhang W 1; Xiao MS 1; Li X 1,4; Li M 5; Wang HZ 1,6; Jiang HY 7; Zhang DF 1,4; Wang JC 7; Ji S 2; Zhang SL 8
刊名	SCHIZOPHRENIA RESEARCH
	2014
卷号	160 期号:1-3 页码:88-96
关键词	Schizophrenia NCAM1 Association Replication ELISA Luciferase assay
通讯作者	ygyaozh@gmail.com
合作状况	其它
英文摘要	Background: Schizophrenia is recognized as a disorder of the brain and neuronal connectivity. The neural cell adhesion molecule 1 (NCAM1) gene plays a crucial role in regulating neuronal connectivity. Methods: We conducted a two-stage association analysis on 17 NCAM1 SNPs in two independent Han Chinese schizophrenia case-control cohorts (discovery sample from Hunan Province: 986 patients and 1040 normal controls; replication sample from Yunnan Province: 564 cases and 547 healthy controls). Allele, genotype and haplotype frequencies were compared between case and control samples. Transcription factor binding site prediction and luciferase reporter assays were employed to assess the potential function of promoter SNPs. We detected developmental changes at the transcriptional level of NCAM1 during neuron differentiation in Macaca mulatta neural progenitor cells (NPC). Serum levels of NCAM1 were measured in 72 cases and 88 controls. Results: A promoter variant, rs2301228, was found to be associated with schizophrenia at the allelic level and was validated in a replication cohort. Luciferase reporter assays demonstrated that risk allele rs2301228-A significantly down-regulated NCAM1 gene transcription compared to the G-allele. Concordantly, schizophrenia patients had a significantly lower level of serum NCAM1 compared to healthy donors. During the NPC neuronal differentiation, NCAM1 mRNA was significantly increased, suggesting a critical role of this gene in neural development. Conclusions: Our results provide direct evidence for NCAM1 as a susceptibility gene for schizophrenia, which offers support to a neurodevelopmental model and neuronal connectivity hypothesis in the onset of schizophrenia.
收录类别	SCI
资助信息	This study was supported by the Strategic Priority Research Program (B) of the Chinese Academy of Sciences (XDB02020000).
语种	英语
内容类型	期刊论文
源URL	[http://159.226.149.26:8080/handle/152453/9250]
专题	昆明动物研究所_重大疾病机理的遗传学昆明动物研究所_动物模型与人类重大疾病机理重点实验室昆明动物研究所_遗传资源与进化国家重点实验室昆明动物研究所_哺乳动物胚胎发育
作者单位	1.Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, China 2.State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China 3.Institute of Mental Health, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China 4.Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Yunnan, China 5.Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA 6.School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, China 7.Department of Psychiatry, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China 8.Coal Mine Mental Hospital of Yunnan Province, Honghe, Yunnan 652402, China 9.Laboratory for Conservation and Utilization of Bio-resource & Key Laboratory for Microbial Resources of the Ministry of Education, Yunnan University, Kunming, Yunnan, China
推荐引用方式 GB/T 7714	Zhang W,Xiao MS,Li X,et al. Promoter variant rs2301228 on the neural cell adhesionmolecule 1 gene confers risk of schizophrenia in Han Chinese[J]. SCHIZOPHRENIA RESEARCH,2014,160(1-3):88-96.
APA	Zhang W.,Xiao MS.,Li X.,Li M.,Wang HZ.,...&Xu L.(2014).Promoter variant rs2301228 on the neural cell adhesionmolecule 1 gene confers risk of schizophrenia in Han Chinese.SCHIZOPHRENIA RESEARCH,160(1-3),88-96.
MLA	Zhang W,et al."Promoter variant rs2301228 on the neural cell adhesionmolecule 1 gene confers risk of schizophrenia in Han Chinese".SCHIZOPHRENIA RESEARCH 160.1-3(2014):88-96.