title: The age at motor symptoms onset in LRRK2-associated Parkinson's disease is affected by a variation in the MAPT locus: a possible interaction.
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.
authors: The Genetic Institute, Tel-Aviv Sourasky Medical Center, 6 Weizmann Street, Tel Aviv, 64239, Israel.
authors: Ziv
authors: Z
authors: Gan-Or
authors: Anat
authors: A
authors: Bar-Shira
authors: Anat
authors: A
authors: Mirelman
authors: Tanya
authors: T
authors: Gurevich
authors: Nir
authors: N
authors: Giladi
authors: Avi
authors: A
authors: Orr-Urtreger
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D000375:Aging / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D006580:Genetic Carrier Screening / Q000379:methods; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics; D006801:Humans; D007585:Jews / Q000235:genetics; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000453:epidemiology* / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D044465:White People / Q000235:genetics; D016875:tau Proteins / Q000235:genetics*
chemical_list: C054369:MAPT protein, human; D016875:tau Proteins; C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases