The +347 C promoter allele up-regulates MAPT expression and is associated with Alzheimer's disease among the Chinese Han.

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.