title: The +347 C promoter allele up-regulates MAPT expression and is associated with Alzheimer's disease among the Chinese Han.
abstract: The microtubule-associated protein tau has been known to be associated with the pathogenesis of Alzheimer's disease (AD). We identified a novel single nucleotide polymorphism (SNP) in the promoter region of the microtubule-associated protein tau gene (MAPT) in Chinese Han population: 347G/C. The samples we analyzed were all identified as H1/H1 genotype; the 347C allele was over-represented in 252 sporadic AD patients (84.3%, P=0.006) when compared with 197 controls (75.1%). The transcriptional activity of SNP in promoter was further investigated using a luciferase reporter assay in two human cell lines, SH-SY5Y and Hela. We demonstrated that the promoter transcriptional activity of the 347 C/C genotype was significantly higher than that of the 347 G/G genotype (SH-SY5Y, P=0.0321; Hela, P=0.0016). Our data suggest that the 347C polymorphism in the promoter of MAPT gene, which is associated with an up-regulation of the gene expression, is a susceptibility factor in sporadic AD.
authors.affiliation: Department of Neurology, Xuan Wu Hospital of the Capital Medical University, Key Neurodegenerative Laboratory of Ministry of Education of the People's Republic of China, Beijing 100053, China.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Sun
authors.forename: Jianping
authors.initials: J
authors.lastname: Jia
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000208:ethnology* / Q000235:genetics* / Q000503:physiopathology; D044466:Asian People / Q000235:genetics*; D002681:China / Q000208:ethnology; D004252:DNA Mutational Analysis; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics; D005787:Gene Frequency / Q000235:genetics; D017930:Genes, Reporter / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D005838:Genotype; D006367:HeLa Cells; D006801:Humans; D008156:Luciferases / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D015533:Transcriptional Activation / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics; D016875:tau Proteins / Q000235:genetics*
chemical_list: D016875:tau Proteins; D008156:Luciferases