The age at motor symptoms onset in LRRK2-associated Parkinson's disease is affected by a variation in the MAPT locus: a possible interaction

J Mol Neurosci. 2012 Mar;46(3):541-4. doi: 10.1007/s12031-011-9641-0. Epub 2011 Sep 6.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age of Onset
  • Aged
  • Aging / genetics*
  • Cohort Studies
  • European Continental Ancestry Group / genetics
  • Female
  • Genetic Carrier Screening / methods
  • Genetic Loci*
  • Genetic Predisposition to Disease / epidemiology
  • Genetic Predisposition to Disease / genetics
  • Genetic Variation / genetics
  • Humans
  • Jews / genetics
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
  • Male
  • Middle Aged
  • Parkinson Disease / epidemiology*
  • Parkinson Disease / genetics*
  • Polymorphism, Single Nucleotide / genetics
  • Protein-Serine-Threonine Kinases / genetics*
  • tau Proteins / genetics*

Substances

  • MAPT protein, human
  • tau Proteins
  • LRRK2 protein, human
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
  • Protein-Serine-Threonine Kinases