Full sequencing and haplotype analysis of MAPT in Parkinson's disease and rapid eye movement sleep behavior disorder

Mov Disord. 2018 Jul;33(6):1016-1020. doi: 10.1002/mds.27385. Epub 2018 May 14.

Abstract

Background: MAPT haplotypes are associated with PD, but their association with rapid eye movement sleep behavior disorder is unclear.

Objective: To study the role of MAPT variants in rapid eye movement sleep behavior disorder.

Methods: Two cohorts were included: (A) PD (n = 600), rapid eye movement sleep behavior disorder (n = 613) patients, and controls (n = 981); (B) dementia with Lewy bodies patients with rapid eye movement sleep behavior disorder (n = 271) and controls (n = 950). MAPT-associated variants and the entire coding sequence of MAPT were analyzed. Age-, sex-, and ethnicity-adjusted analyses were performed to examine the association between MAPT, PD, and rapid eye movement sleep behavior disorder.

Results: MAPT-H2 variants were associated with PD (odds ratios: 0.62-0.65; P = 0.010-0.019), but not with rapid eye movement sleep behavior disorder. In PD, the H1 haplotype odds ratio was 1.60 (95% confidence interval: 1.12-2.28; P = 0.009), and the H2 odds ratio was 0.68 (95% confidence interval: 0.48-0.96; P = 0.03). The H2/H1 haplotypes were not associated with rapid eye movement sleep behavior disorder.

Conclusions: Our results confirm the protective effect of the MAPT-H2 haplotype in PD, and define its components. Furthermore, our results suggest that MAPT does not play a major role in rapid eye movement sleep behavior disorder, emphasizing different genetic background than in PD in this locus. © 2018 International Parkinson and Movement Disorder Society.

Keywords: MAPT; Parkinson's disease; REM sleep behavior disorder; genetics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Cohort Studies
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease*
  • Genotype
  • Humans
  • Lewy Body Disease / complications
  • Lewy Body Disease / genetics
  • Male
  • Middle Aged
  • Parkinson Disease / genetics*
  • Polymorphism, Single Nucleotide / genetics*
  • Principal Component Analysis
  • REM Sleep Behavior Disorder / genetics*
  • tau Proteins / genetics*

Substances

  • MAPT protein, human
  • tau Proteins