Journal
JOURNAL OF MOLECULAR NEUROSCIENCE
Volume 46, Issue 3, Pages 541-544Publisher
HUMANA PRESS INC
DOI: 10.1007/s12031-011-9641-0
Keywords
Parkinson's disease; MAPT; Tau; LRRK2
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Funding
- Tel Aviv Sourasky Medical Center
- Kahn Foundation
- Israeli Ministry of Health [3-4893]
- Israel Science Foundation [1922/08]
- National Parkinson Foundation, USA
- Wolfson Foundation
- Michael J. Fox Foundation
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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.
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