TY - JOUR
T1 - The age at motor symptoms onset in LRRK2-associated Parkinson's disease is affected by a variation in the MAPT locus
T2 - A possible interaction
AU - Gan-Or, Ziv
AU - Bar-Shira, Anat
AU - Mirelman, Anat
AU - Gurevich, Tanya
AU - Giladi, Nir
AU - Orr-Urtreger, Avi
N1 - Funding Information:
Acknowledgments This work was supported by Tel Aviv Sourasky Medical Center Grant of Excellence, by Kahn Foundation, by the Chief Scientist of the Israeli Ministry of Health (grant No. 3–4893), by the Legacy Heritage Biomedical Science Partnership Program of the Israel Science Foundation (grant No.1922/08), by the National Parkinson Foundation, USA, and by Wolfson and Michael J. Fox Foundations. This work was performed in partial fulfillment of the requirements for a Ph.D. degree of Ziv Gan-Or, Sackler Faculty of medicine, Tel Aviv University, Israel.
PY - 2012/3/1
Y1 - 2012/3/1
N2 - 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.
AB - 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.
KW - LRRK2
KW - MAPT
KW - Parkinson's disease
KW - Tau
UR - http://www.scopus.com/inward/record.url?scp=84859159465&partnerID=8YFLogxK
U2 - 10.1007/s12031-011-9641-0
DO - 10.1007/s12031-011-9641-0
M3 - Article
C2 - 21898123
AN - SCOPUS:84859159465
SN - 0895-8696
VL - 46
SP - 541
EP - 544
JO - Journal of Molecular Neuroscience
JF - Journal of Molecular Neuroscience
IS - 3
ER -