title: Converging evidence implicates the dopamine D3 receptor gene in vulnerability to schizophrenia.
abstract: 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.
authors: Department of Psychiatry, Tsinghua University Yuquan Hospital, Beijing, China.
authors: Fuquan
authors: F
authors: Zhang
authors: Hua
authors: H
authors: Fan
authors: Yong
authors: Y
authors: Xu
authors: Kerang
authors: K
authors: Zhang
authors: Xuezhu
authors: X
authors: Huang
authors: Yan
authors: Y
authors: Zhu
authors: Manqiu
authors: M
authors: Sui
authors: Gaoxiang
authors: G
authors: Sun
authors: Kun
authors: K
authors: Feng
authors: Bo
authors: B
authors: Xu
authors: Xiaoqian
authors: X
authors: Zhang
authors: Zhonghua
authors: Z
authors: Su
authors: Chunqing
authors: C
authors: Peng
authors: Pozi
authors: P
authors: Liu