Motor progression of Parkinson's disease with the leucine-rich repeat kinase 2 G2019S mutation

Mov Disord. 2014 Jul;29(8):1057-60. doi: 10.1002/mds.25931. Epub 2014 Jun 5.

Abstract

Introduction: In this retrospective study, we compared motor disease progression in Ashkenazi-Jewish (AJ) Parkinson's disease (PD) patients carrying the LRRK2*G2019S mutation with that of noncarriers.

Methods: Consecutive PD patients were recruited between 2004 and 2011. Disease progression of carriers versus noncarriers was compared using survival analysis, where the end-point was the time from PD onset to reaching Hoehn and Yahr stage 3 (HY3).

Results: Overall, 405 AJ PD patients (males = 241[60%]) were genotyped, of whom 60 (males = 30) were LRRK2*G2019S mutation carriers. Time to HY3 did not differ significantly between mutation carriers and noncarriers (hazard ratio = 1.21, 95%CI = 0.83-1.77, P = 0.33). Age at PD onset was younger for carriers than for noncarriers (59.1 ± 9.8 vs. 63.2 ± 12.0 years, respectively; P = 0.005). In both groups, young age at onset was strongly associated with longer time to HY3, (P < 0.001).

Conclusion: The LRRK2*G2019S mutation status has no discernible effect on the rate of motor disease progression in AJ PD patients.

Keywords: LRRK2; Parkinson's disease; disease progression; genetic.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Disease Progression
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease / genetics*
  • Genotype
  • Glycine / genetics*
  • Humans
  • Jews / genetics
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
  • Male
  • Middle Aged
  • Mutation / genetics*
  • Parkinson Disease / ethnology
  • Parkinson Disease / genetics*
  • Parkinson Disease / physiopathology*
  • Protein Serine-Threonine Kinases / genetics*
  • Retrospective Studies

Substances

  • LRRK2 protein, human
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
  • Protein Serine-Threonine Kinases
  • Glycine