摘要
目的探讨Nicastrin(NCSTN)基因启动子区多态性与散发阿尔茨海默病(sporadic Alzheimer s dis-ease,SAD)发病的关系及其机制。方法用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)和直接测序的方法对中国北方汉族359例SAD患者和331名正常对照者NCSTN基因启动子区单核苷酸多态性位点(SNP)进行筛查,基因分型后,进行病例对照-相关分析。构建三种不同基因型启动子质粒,通过双荧光报告基因系统检测不同启动子质粒的转录活性。结果①中国北方人群中的NCSTN基因启动子区ATG上游2245 bp范围内存在3个SNP:-1216C/A(rs2147471),-796T/G(rs10752637)和-436C/T(rs1324738);②-1216C/A和-796T/G的基因型频率在各自的SAD组和正常对照组中的分布差异有统计学意义;③三种启动子质粒的转录活性差异无统计。结论NCSTN启动子区SNP:-796T/G和-1216C/A,与SAD的发病具有相关性,但未发现这两个位点具有病理学功能。
Objective To study the association between promoter variations of nicastrin （NCSTN） gene and and sporadic Alzheimer＇s disease （SAD） in Chinese Han population. Methods The single nucleotide polymorphisms （SNPs） in the NCSTN proximal promoter were detected by PCR-RFLP or direct sequencing in 359 SAD patients and 331 healthy controls in a Chinese Han population. Transcriptional activity of promoters was evaluated using luciferase reporter assay. Resuits ①Three SNPs in NCSTN proximal promoter： - 1216C/A（rs2147471 ）, - 796T/G（rs10752637） and - 436C/T （rs1324738） were identified. ② There were statistical differences in the distribution of genotypes of - 1216C/A and - 796T/G between SAD and controls. ③ There were no significant differences in the transcriptional activity among three SNPs. Conclusions Our investigation suggests that three novel NCSTN promoter SNPs are not associated with SAD.
出处
《中国神经精神疾病杂志》
CAS
CSCD
北大核心
2009年第3期159-163,共5页
Chinese Journal of Nervous and Mental Diseases
基金
十一五国家科技支撑计划基金资助项目(编号:2006BAI02B01)
国家973基金资助项目(编号:2006CB500700)
北京自然科学基金重点资助项目(编号:7071004)
北京市属市管高校人才强教计划项目
