Association of the MAPT locus with Parkinson’s disease

Background and purpose:  Whilst an association between the tau gene (MAPT)-containing H1 haplotype and supranuclear gaze palsy (PSP) has long been recognized, the effect of H1 on risk for Parkinson’s disease (PD) has remained more contentious. Methods:  Herein, we examined the association of H1 and PD in three Caucasian PD patient–control series from Ireland, Norway, and the US (combined: n = 2619), by genotyping two H1/H2 single nucleotide polymorphisms (SNPs) in MAPT (rs1052553) and in the Saitohin gene (rs62063857) and one H1-specific SNP (rs242557). Results:  We identified a significant association between H1/H2 and risk of PD (rs1052553 OR: 1.43, CI: 1.23–1.64; rs62063857 OR: 1.45, CI: 1.27–1.67), but no effect of the H1-specific SNP rs242557 (OR: 0.92, CI: 0.82–1.03). Conclusions:  Our findings show that the H1 haplotype is a significant risk factor for PD. However, one H1-specific SNP (rs242557) previously implicated in PSP did not alter the risk of PD, indicating that distinct H1 sub-haplotypes probably drive the associations with PD and PSP.