Hawi Z, McCabe U, Straub R E, O'Neill A, Kendler K S, Walsh D, Gill M
Department of Psychiatry, Trinity College, Dublin, Ireland. zhhawi@.tcd.ie(2HHAWI)
Mol Psychiatry. 1998 Mar;3(2):150-5. doi: 10.1038/sj.mp.4000362.
The dopamine D3 (DRD3) receptor gene has been implicated in the aetiology of schizophrenia as a candidate gene since it combines both the dopamine receptor and limbic hypotheses of the disease. Previous association studies of a DRD3/MscI polymorphism suggested an increased frequency of homozygosity at the DRD3 receptor gene in schizophrenia. Homozygosity appeared to be particularly frequent in male patients, individuals with family history of the disease and in good responders to neuroleptic treatment. Many studies have since examined this polymorphism and have altered or extended the original homozygosity hypothesis. In this study, we have investigated the distribution of the DRD3/MscI polymorphism in 198 Irish schizophrenic patients and 235 ethnically matched controls. Patients and controls showed-similar allele and genotype frequencies. Furthermore, linkage analysis using two microsatellite markers flanking the DRD3 gene was performed on 265 Irish schizophrenic families, with substantially negative results. Our findings, in combination with a review of previous studies do not support a role for the DRD3/MscI polymorphism in the pathogenesis of schizophrenia.
多巴胺D3（DRD3）受体基因一直作为候选基因被认为与精神分裂症的病因学有关，因为它结合了该疾病的多巴胺受体假说和边缘系统假说。先前对DRD3/MscI多态性的关联研究表明，精神分裂症患者中DRD3受体基因的纯合子频率增加。纯合子在男性患者、有家族病史的个体以及对神经阻滞剂治疗反应良好的个体中似乎尤为常见。此后，许多研究对这种多态性进行了检测，并对最初的纯合子假说进行了修改或扩展。在本研究中，我们调查了198名爱尔兰精神分裂症患者和235名种族匹配的对照中DRD3/MscI多态性的分布情况。患者和对照显示出相似的等位基因和基因型频率。此外，我们对265个爱尔兰精神分裂症家族进行了使用位于DRD3基因两侧的两个微卫星标记的连锁分析，结果基本为阴性。我们的研究结果，结合对先前研究的综述，不支持DRD3/MscI多态性在精神分裂症发病机制中的作用。
