Converging evidence implicates the dopamine D3 receptor gene in vulnerability to schizophrenia
Converging evidence implicates the dopamine D3 receptor gene in vulnerability to schizophrenia
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DOI：
10.1002/ajmg.b.31203
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发表时间：
2011-07
期刊：
影响因子：
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通讯作者：
Fuquan Zhang;H. Fan;Yong Xu;Kerang Zhang;Xuezhu Huang;Yan Zhu;Manqiu Sui;Gao-Xiang Sun;Kun Feng;Bo Xu;Xiao-Qian Zhang;Zhonghua Su;C. Peng;Po-Zi Liu
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文献类型：
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作者：
Fuquan Zhang;H. Fan;Yong Xu;Kerang Zhang;Xuezhu Huang;Yan Zhu;Manqiu Sui;Gao-Xiang Sun;Kun Feng;Bo Xu;Xiao-Qian Zhang;Zhonghua Su;C. Peng;Po-Zi Liu
多巴胺D3受体参与了精神分裂症(SZ)的病理生理过程。多巴胺D3受体基因(DRD3)第9密码子上的甘氨酸到丝氨酸的多态性rs6280因其与SZ的关联而被广泛研究，但结果相互矛盾。据报道，与正常对照组相比，深圳地区DRD3mRNA水平也发生了变化。此外，有研究表明，DRD3在欧洲人群中受到最近的正向选择。为了从不同方面探讨DRD3在SZ中的潜在作用，我们进行了三项研究。首先，我们在685名SZ患者和768名正常对照中检测了rs6280与SZ的遗传关联。其次，我们检测了37名患者和37名对照组外周血白细胞中DRD3的mRNA水平。最后，我们调查了最近在东亚人群中DRD3可能的正选择。因此，我们观察到rs6280的基因分布在名义上与SZ相关(P=0.045)，祖先的CC基因型在SZ患者中显著过度表达。患者组DRD3mRNA水平显著低于对照组(P=5.91E−5)。在东亚人群中，rs6280的C等位基因可能受到最近的正选择(P<；0.001)的影响。综上所述，我们的结果表明，DRD3基因可能是自然选择下的一个基因，可能与中国汉族人对SZ的易感性有关。这些发现可能会进一步增加DRD3作为精神分裂症风险基因的数据。©2011 Wiley-Liss，Inc.
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. © 2011 Wiley‐Liss, Inc.