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

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

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 leucinerich 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.

Original languageEnglish
Pages (from-to)541-544
Number of pages4
JournalJournal of Molecular Neuroscience
Volume46
Issue number3
DOIs
StatePublished - 1 Mar 2012
Externally publishedYes

Keywords

  • LRRK2
  • MAPT
  • Parkinson's disease
  • Tau

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