多巴胺受体D5基因5’端单核苷酸多态性与偏执型精神分裂症的关联及对基因表达的影响  

Single nucleotide polymorphisms in the 5’-flanking region of dopamine receptor D5 affect its gene expression and are associated with paranoid schizophrenia

作　　者：张静静 邢佳鑫[1] 吴雪 许凤玲 宣金锋 姚军 王保捷 ZHANG Jingjing;XING Jiaxin;WU Xue;XU Fengling;XUAN Jinfeng;YAO Jun;WANG Baojie(Department of Forensic Genetics,School of Forensic Medicine,China Medical University,Shenyang 110122,China;The Core Laboratory for Public Health Science and Practice,The First Hospital,China Medical University,Shenyang 110001,China)

机构地区：[1]中国医科大学法医学院法医物证学教研室,沈阳110122 [2]中国医科大学附属第一医院中心实验室,沈阳110001

出　　处：《中国医科大学学报》2020年第2期102-106,共5页Journal of China Medical University

基　　金：国家自然科学基金(81671872);辽宁省自然科学基金(20170541019)

摘　　要：目的进一步探讨多巴胺受体D5(DRD5)基因在偏执型精神分裂症发病机制中的作用,分析rs77434921和rs2076907位点以及5’端序列对基因表达的影响。方法将不同单倍型分别转染HEK293细胞和SK-N-SH细胞,进行荧光素酶报告分析,并提取总细胞RNA,进行实时定量PCR分析。结果在HEK293和SK-N-SH细胞中,与其他3种单倍型相比,G-G单倍型的相对荧光素酶活性均无显著变化。然而在后续研究中发现,-1599^-934这段序列在维持转录水平中发挥作用,而+82^+564这段序列发挥下调转录水平的作用。结论未能证实位于DRD5基因上的rs2076907和rs77434921这2个单核苷酸多态性位点调控基因的表达,证实了其5’端的一部分区域对基因表达有显著影响。Objective To investigate the role of dopamine receptor D5(DRD5)gene in the pathogenesis of paranoid schizophrenia and to analyze the effects of the rs77434921 and rs2076907 loci and 5’-end sequences on its gene expression.Methods Different haplotypes were transfected into HEK293 and SK-N-SH cells,luciferase reporter assays were performed,and total cellular RNA was extracted for real-time quantitative PCR analysis.Results In both HEK293 and SK-N-SH cells,there were no significant changes in the relative luciferase activity of the G-G haplotype compared with that of the other three haplotypes.However,in subsequent tests,it was found that the sequence from-1599 to-934 played a role in the maintenance of transcriptional levels,and the sequence from+82 to+564 played a role in down-regulating the transcription.Conclusion The effect of the two single nucleotide polymorphisms rs2076907 and rs77434921 located in the regulatory region of the DRD5 gene could not be confirmed;however,it was confirmed that a part of the 5’-end had a significant effect on gene expression.

关 键 词：法医学 多巴胺受体D5基因 精神分裂症 

分 类 号：R749.3[医药卫生—神经病学与精神病学]