Nimgaonkar V L, Sanders A R, Ganguli R, Zhang X R, Brar J, Hogge W, Fann W E, Patel P I, Chakravarti A
Department of Psychiatry, University of Pittsburgh School of Medicine, Pennsylvania, USA.
Am J Med Genet. 1996 Nov 22;67(6):505-14. doi: 10.1002/(SICI)1096-8628(19961122)67:6<505::AID-AJMG1>3.0.CO;2-G.
Using a case-control design, an association of schizophrenia with the dopamine D3 receptor gene (D3RG) locus was investigated. Initial analysis of pooled results from published studies revealed a significant excess of individuals homozygous for either allele among the patients. The association was next tested in two cohorts ascertained independently at Pittsburgh, Pennsylvania and at Houston, Texas. The Pittsburgh sample was comprised of patients with schizophrenia (DSM-III-R) (n = 130). The controls belonged to two groups: adults screened for the absence of substance abuse or major psychiatric illness (n = 128), and neonates (n = 160). Multivariate analysis suggested an association with allele 1 of the biallelic D3RG polymorphism in comparison with the adult, but not the neonatal, controls. The association was most marked among Caucasian patients with a family history of schizophrenia (odds ratio 13.69, confidence intervals 1.80, 104.30). Survival analysis suggested an earlier age of onset among male patients homozygous for allele 2. The Houston cohort included Caucasian patients with schizophrenia or schizoaffective disorder (DSM-III-R criteria, n = 50), and normal controls matched for gender (n = 51). In this group, no significant associations were noted among all the patients or among subgroups of patients based on family history or age of onset. Possible reasons for the discordant results are discussed.
采用病例对照设计，对精神分裂症与多巴胺D3受体基因（D3RG）位点的关联进行了研究。对已发表研究的汇总结果进行的初步分析显示，患者中任一等位基因纯合子个体显著过多。接下来在宾夕法尼亚州匹兹堡和得克萨斯州休斯敦独立确定的两个队列中对该关联进行了检验。匹兹堡样本包括精神分裂症患者（DSM-III-R）（n = 130）。对照组分为两组：经筛查无药物滥用或重大精神疾病的成年人（n = 128）和新生儿（n = 160）。多变量分析表明，与成年对照组相比，双等位基因D3RG多态性的等位基因1与精神分裂症有关联，但与新生儿对照组无关。这种关联在有精神分裂症家族史的白种患者中最为明显（优势比13.69，置信区间1.80，104.30）。生存分析表明，等位基因2纯合的男性患者发病年龄较早。休斯敦队列包括患有精神分裂症或分裂情感性障碍的白种患者（DSM-III-R标准，n = 50），以及按性别匹配的正常对照组（n = 51）。在该组中，所有患者之间或根据家族史或发病年龄划分的患者亚组之间均未发现显著关联。文中讨论了结果不一致的可能原因。
