Journal of Molecular Neuroscience

, Volume 46, Issue 3, pp 541–544

The Age at Motor Symptoms Onset in LRRK2-Associated Parkinson's Disease is Affected by a Variation in the MAPT Locus: A Possible Interaction

  • Ziv Gan-Or
  • Anat Bar-Shira
  • Anat Mirelman
  • Tanya Gurevich
  • Nir Giladi
  • Avi Orr-Urtreger
Article

DOI: 10.1007/s12031-011-9641-0

Cite this article as:
Gan-Or, Z., Bar-Shira, A., Mirelman, A. et al. J Mol Neurosci (2012) 46: 541. doi:10.1007/s12031-011-9641-0

Abstract

The current paradigm on Parkinson's disease (PD) pathogenesis and course suggests the involvement of multiple genes and the interaction between them. Recently, it was reported that a variation (rs2435207) in the MAPT gene region influenced the age of motor symptoms onset (AO) in 44 PD patients from 19 families, carriers of leucine-rich repeat kinase 2 (LRRK2) mutations, all of European and North American origin. To examine whether genetic factors within the MAPT locus exert a similar effect on AO in a different population of LRRK2-associated PD patients, 99 unrelated Ashkenazi patients with the LRRK2 p.G2019S mutation were analyzed. Three SNPs in the MAPT region were studied, rs393152, rs2435207, and rs11079727; the latter is located in the first intron of MAPT. Among carriers of the single LRRK2 p.G2019S mutation that did not carry a founder Ashkenazi GBA mutation too (n = 84), the AO in minor rs11079727 A allele carriers (C/A genotype) was significantly older (62.5 ± 10.6 years) compared to the AO (55.7 ± 11.6) among carriers of the C/C genotype (p = 0.025). Our results further support a possible interaction between genetic factors in the MAPT region and the LRRK2 gene, which influence the clinical course of PD patients.

Keywords

Parkinson’s disease MAPT Tau LRRK2 

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Ziv Gan-Or
    • 1
    • 3
  • Anat Bar-Shira
    • 1
  • Anat Mirelman
    • 2
  • Tanya Gurevich
    • 2
    • 3
  • Nir Giladi
    • 2
    • 3
  • Avi Orr-Urtreger
    • 1
    • 3
  1. 1.The Genetic Institute, Tel-Aviv Sourasky Medical CenterTel AvivIsrael
  2. 2.Movement Disorders Unit, Department of NeurologyTel-Aviv Sourasky Medical CenterTel-AvivIsrael
  3. 3.The Sackler Faculty of MedicineTel-Aviv UniversityTel-AvivIsrael

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