Spurlock G, Williams J, McGuffin P, Aschauer H N, Lenzinger E, Fuchs K, Sieghart W C, Meszaros K, Fathi N, Laurent C, Mallet J, Macciardi F, Pedrini S, Gill M, Hawi Z, Gibson S, Jazin E E, Yang H T, Adolfsson R, Pato C N, Dourado A M, Owen M J
Department of Psychological Medicine, University of Wales College of Medicine Health Park, Cardiff, United Kingdom.
Am J Med Genet. 1998 Feb 7;81(1):24-8. doi: 10.1002/(sici)1096-8628(19980207)81:1<24::aid-ajmg5>3.0.co;2-n.
As part of the European Multicentre Association Study of Schizophrenia (EMASS), we studied polymorphisms in the dopamine DRD2 and DRD3 receptor genes. The EMASS collaboration was established to create a large, statistically powerful sample of schizophrenic patients and controls from different European centres. Previous studies have suggested associations between schizophrenia and the Ser311Cys polymorphism in exon 7 of the dopamine DRD2 receptor gene [Arinami et al., (1994): Lancet 343:703-704] and a polymorphism Ser9gly in exon 1 of the dopamine DRD3 receptor gene [Crocq et al. (1992): J Med Genet 29:858-860]. We tested for these associations in samples of 373 and 413, and 311 and 306 patients and controls, respectively. We found no evidence for allelic association between schizophrenia and the Cys311 variant of the DRD2 receptor gene and no homozygotes for this variant were observed by any group. However, an excess of homozygotes for both alleles of the DRD3 polymorphism was observed in schizophrenic patients (chi2 = 8.54, P = 0.003, odds ratio = 1.64, 95% CI = 1.18-2.29). We also observed a significant excess of the 1-1 (Ser9Ser) genotype (chi2 = 8.13, P = 0.004, odds ratio = 1.7, 95% CI = 1.18-2.4). No evidence of heterogeneity between samples was detected and there was no evidence of an allelic association. These findings suggest that the rare Cys311 variant in exon 7 of the DRD2 receptor gene does not play a role in the pathogenesis of schizophrenia in European populations. Currently, our results do support the previous findings of an association between increased homozygosity of the Ser/Gly variant of the Dopamine D3 receptor gene and schizophrenia.
作为欧洲多中心精神分裂症协会研究（EMASS）的一部分，我们研究了多巴胺DRD2和DRD3受体基因的多态性。EMASS合作项目旨在从不同欧洲中心创建一个大型、具有统计学效力的精神分裂症患者和对照样本。先前的研究表明，精神分裂症与多巴胺DRD2受体基因第7外显子中的Ser311Cys多态性[有栖浪等，（1994年）：《柳叶刀》343:703 - 704]以及多巴胺DRD3受体基因第1外显子中的Ser9gly多态性[克罗克等（1992年）：《医学遗传学杂志》29:858 - 860]之间存在关联。我们分别在373例和413例、311例和306例患者及对照样本中对这些关联进行了检测。我们未发现精神分裂症与DRD2受体基因的Cys311变体之间存在等位基因关联的证据，且任何组均未观察到该变体的纯合子。然而，在精神分裂症患者中观察到DRD3多态性两个等位基因的纯合子过多（卡方 = 8.54，P = 0.003，优势比 = 1.64，95%可信区间 = 1.18 - 2.29）。我们还观察到1 - 1（Ser9Ser）基因型显著过多（卡方 = 8.13，P = 0.004，优势比 = 1.7，95%可信区间 = 1.18 - 2.4）。未检测到样本间存在异质性的证据，也没有等位基因关联的证据。这些发现表明，DRD2受体基因第7外显子中罕见的Cys311变体在欧洲人群精神分裂症的发病机制中不起作用。目前，我们的结果确实支持了先前关于多巴胺D3受体基因Ser/Gly变体纯合性增加与精神分裂症之间存在关联的研究结果。
