Different MAPT haplotypes are associated with Parkinson's disease and progressive supranuclear palsy

The H1 MAPT haplotype in the 17q21 chromosomal region has been associated with several neurodegenerative diseases. Some reports have suggested that there is an association between genetic variants within the H1 haplotype with Parkinson's disease (PD), progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). Here we report a genetic association study using seven SNPs located along the 17q21 region, in PD patients and controls. In addition, we compared these results with a dataset of previously published PSP/CBD patients from the same population. Our results show that the H1-rs242557G allele sub-haplotype is increased in PD (p = 0.005), while the H1-rs242557A allele sub-haplotype is increased in PSP/CBD (p = 0.0002), comparing to controls. The rs242557 polymorphism could act modulating the phenotypic expressivity of the H1 risk on these parkinsonisms. The location of this polymorphism in the 5′ regulatory region of MAPT gene suggests the presence of a functional mechanism involved in the variation of MAPT expression levels.