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学科主题: 精神卫生
题名:
Converging Evidence Implicates the Dopamine D3 Receptor Gene in Vulnerability to Schizophrenia
作者: Zhang, Fuquan1,2; Fan, Hua3; Xu, Yong4; Zhang, Kerang4; Huang, Xuezhu1; Zhu, Yan1; Sui, Manqiu1; Sun, Gaoxiang1; Feng, Kun1; Xu, Bo1; Zhang, Xiaoqian1; Su, Zhonghua5; Peng, Chunqing6; Liu, Pozi1
关键词: schizophrenia ; DRD3 ; rs6280 ; positive selection
刊名: AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS
发表日期: 2011-07-01
DOI: 10.1002/ajmg.b.31203
卷: 156B, 期:5, 页:613-619
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Genetics & Heredity ; Psychiatry
研究领域[WOS]: Genetics & Heredity ; Psychiatry
关键词[WOS]: RECENT POSITIVE SELECTION ; D-3 RECEPTOR ; MESSENGER-RNA ; ASSOCIATION ; POLYMORPHISM ; EXPRESSION ; METAANALYSIS ; HAPLOTYPE ; GENOME ; DRD3
英文摘要:

The dopamine D3 receptor has been implicated in the pathophysiology of schizophrenia (SZ). A glycine-to-serine polymorphism at codon 9 of the dopamine D3 receptor gene (DRD3), rs6280, has been widely studied for its association with SZ, but with conflicting results. Altered levels of DRD3 mRNA have also been reported in SZ compared with normal controls. Moreover, it has been suggested that DRD3 is subject to recent positive selection in European populations. To explore the potential role of DRD3 in SZ from these various aspects, we conducted a threefold study. First, we tested the genetic association of rs6280 with SZ in 685 SZ patients and 768 normal controls. Second, we examined DRD3 mRNA levels in peripheral leukocytes in a subset of 37 patients and 37 controls. Finally, we investigated the possible recent positive selection on DRD3 in an East Asian population. Consequently, we observed that the genotypic distribution of rs6280 was nominally associated with SZ (P = 0.045), with the ancestral CC genotype being significantly over-represented in SZ patients. DRD3 mRNA levels were significantly lower in patients than in controls (P = 5.91E - 5). The derived C-allele of rs6280 might have been subject to recent positive selection (P < 0.001) in the East Asian population. Taken together, our results suggest that DRD3, a gene possibly under natural selection, might be involved in vulnerability to SZ in the Han Chinese population. These findings may further add to the body of data implicating DRD3 as a schizophrenia risk gene. (C) 2011 Wiley-Liss, Inc.

语种: 英语
所属项目编号: 30570430 ; 81000583 ; 81000578 ; 20240000518
项目资助者: National Natural Science Foundation of China ; Tsinghua Yu-Yuan Medical Sciences Fund
WOS记录号: WOS:000291945400012
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/66071
Appears in Collections:北京大学精神卫生研究所_期刊论文

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作者单位: 1.Peking Univ, Inst Mental Hlth, Beijing 100871, Peoples R China
2.Second Affiliated Hosp, Jining Med Coll, Jining, Peoples R China
3.Tsinghua Univ, Yuquan Hosp, Dept Psychiat, Beijing 100049, Peoples R China
4.Capital Med Univ, Dept Psychiat, Beijing Anding Hosp, Beijing, Peoples R China
5.Shanxi Med Univ, Hosp 1, Dept Psychiat, Taiyuan, Peoples R China
6.Nanhua Univ, Affiliated Hosp 1, Clin Psychol Sect, Hengyang, Peoples R China

Recommended Citation:
Zhang, Fuquan,Fan, Hua,Xu, Yong,et al. Converging Evidence Implicates the Dopamine D3 Receptor Gene in Vulnerability to Schizophrenia[J]. AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS,2011,156B(5):613-619.
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