Department of Psychiatry, National Taiwan University Hospital, Taipei, Taiwan.
J Hum Genet. 2013 Apr;58(4):229-32. doi: 10.1038/jhg.2012.157. Epub 2013 Jan 31.
Previous studies have reported significant associations between schizophrenia and the dopamine receptor D2 gene (DRD2) variants. The relationships between DRD2 and clinical phenotypes are of particular interest because DRD2 has been shown to associate with treatment response and prefrontal dopamine transmission. Glatt et al. reported significant associations between schizophrenia and DRD2 variants (two single-nucleotide polymorphisms (SNPs) rs1079727 and rs2283265, and two haplotypes, block 3 (rs1079727(A)-rs2440390(C)-rs2283265(G)) and block 4 (rs1801028(G)-rs1110977(A)-rs1124492(C)-rs2734841 (T))) in 2408 Han Chinese individuals in Taiwan. To further investigate the relationships between the SNPs/haplotypes of DRD2 and clinical symptoms and neuropsychological function, we compared the quantitative phenotypes in patients with risk alleles/haplotypes and those without. The results showed that the A allele of rs1079727, G allele of rs2283265, A allele of rs1124492 and the risk haplotype (A-C-G) of block 3 were associated with more severe negative symptoms. With regard to neuropsychological performance, the risk haplotype (G-A-C-T) of block 4 was associated with poorer performance in the sustained attention task. Our results imply that the genetic variants of DRD2 might not only have a role in susceptibility to schizophrenia, but also influence the phenotypes of negative symptoms and sustained attention in schizophrenia. This association warrants further validation.
先前的研究报道了精神分裂症与多巴胺受体 D2 基因（DRD2）变异之间存在显著关联。DRD2 与临床表型之间的关系特别有趣，因为 DRD2 与治疗反应和前额叶多巴胺传递有关。Glatt 等人报道了精神分裂症与 DRD2 变异（两个单核苷酸多态性（SNP）rs1079727 和 rs2283265，以及两个单倍型，第 3 块（rs1079727(A)-rs2440390(C)-rs2283265(G))和第 4 块（rs1801028(G)-rs1110977(A)-rs1124492(C)-rs2734841 (T)))在台湾的 2408 名汉族个体中存在显著关联。为了进一步研究 DRD2 的 SNP/单倍型与临床症状和神经心理学功能之间的关系，我们比较了携带风险等位基因/单倍型和不携带风险等位基因/单倍型的患者的定量表型。结果表明，rs1079727 的 A 等位基因、rs2283265 的 G 等位基因、rs1124492 的 A 等位基因和第 3 块的风险单倍型（A-C-G）与更严重的阴性症状相关。关于神经心理学表现，第 4 块的风险单倍型（G-A-C-T）与持续注意力任务表现较差相关。我们的结果表明，DRD2 的遗传变异不仅可能与精神分裂症的易感性有关，而且可能影响精神分裂症阴性症状和持续注意力的表型。这种关联需要进一步验证。
