多巴胺D1受体基因与精神分裂症患者症状数量性状的关联分析

Association analysis between dopamine D1 receptor gene and symptom quantitative trait of schizophrenia

目的探讨多巴胺D1受体基因（DRD1）与精神分裂症患者症状数量性状的关联。方法2006年1月至2007年12月在上海交通大学医学院附属精神卫生中心收集211例精神分裂症患者和247名健康对照者的临床资料及外周静脉血并提取DNA，采用TaqMan荧光探针SNP基因分型技术对DRD1基因的5个标签单核苷酸多态性（rs4532、rs5326、rs2168631、rs6882300及rs267418）进行检查，使用阳性和阴性症状量表（PANSS）评定患者疾病表型的数量性状。结果患者组与对照组间DRD1基因5个标签SNP的基因型及等位基因频率分布的差异无统计学意义（Ps〉0．05）；rs4532-rs5326之间存在连锁不平衡（D’=0．84）；单体型分析显示各单体型分布频率差异在病例组与对照组间差异无统计学意义（Ps〉0．05）；携带rs4532G等位基因患者的阴性症状分显著高于不携带G等位基因患者[GG＋GA型（20．3±3．3）分，AA型（18．2±3．9）分，P〈0．01]。结论DRD1基因rs4532位点可能与精神分裂症阴性症状的数量性状存在关联。

Objective To explore the relationship between dopamine D1 receptor gene （DRD1） and symptom quantitative trait of schizophrenia. Methods Peripheral blood samples were collected from 211 schizophrenics and 247 healthy controls at our center. Five tag SNPs （ single nucleotide polymorphisms） （rs4532, rs5326, rs2168631, rs6882300 ＆ rs267418） within DRD1 gene were genotyped by TaqMan SNP genotyping assay. The positive and negative syndrome scale （PANSS） was used to quantify the phenotypes of schizophrenia. Results No significant differences existed in the frequencies of genotypes and alleles of DRD1 gene between the schizophrenics and normal controls （ Ps 〉 0.05 ） ; strong linkage disequilibrium was observed between rs4532 and rs5326 （D＇= 0.84） ; no significant difference of haplotypic distribution was identified between the patients and controls （ Ps 〉 0.05 ） ; the patients with rs4532G allele had a higher negative subscale score than those without G allele （20.3 ± 3.3 vs 18.2 ± 3.9, P 〈 0.01 ）. Conclusion The rs4532 within DRD1 gene may be associated with negative symptom quantitative trait in schizophrenia.