Association of the MAPT locus with Parkinson's disease

Eur J Neurol. 2010 Mar;17(3):483-6. doi: 10.1111/j.1468-1331.2009.02847.x. Epub 2009 Nov 12.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Case-Control Studies
  • Female
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Genotype
  • Haplotypes
  • Humans
  • Ireland
  • Male
  • Norway
  • Parkinson Disease / genetics*
  • Polymorphism, Single Nucleotide
  • Risk Factors
  • Sequence Analysis, DNA
  • Supranuclear Palsy, Progressive / genetics
  • United States
  • White People / genetics
  • tau Proteins / genetics*

Substances

  • MAPT protein, human
  • STH protein, human
  • tau Proteins