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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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 - Mar 2012

Funding

FundersFunder number
Legacy Heritage Biomedical Science Partnership Program of the Israel Science Foundation1922/08
Michael J. Fox Foundation for Parkinson's Research
National Parkinson Foundation
Esther B. Kahn Charitable Foundation
Ministry of Health, State of Israel3–4893

    Keywords

    • LRRK2
    • MAPT
    • Parkinson's disease
    • Tau

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