Clinical profiles of Parkinson's disease associated with common leucine-rich repeat kinase 2 and glucocerebrosidase genetic variants in Chinese individuals

Neurobiol Aging. 2014 Mar;35(3):725.e1-6. doi: 10.1016/j.neurobiolaging.2013.08.012. Epub 2013 Oct 3.

Abstract

Clinical profiles of Parkinson's disease (PD) related to LRRK2 (LRRK2-PD), and GBA (GBA-PD) genes have not been reported in Chinese individuals. In this study, we have investigated motor and non-motor aspects in 1638 Chinese PD patients who carried LRRK2 G2385R or R1628P (LRRK2-PD, n = 223), GBA L444P variant (GBA-PD, n = 49), or none of the variants (idiopathic PD [IPD], n = 1366). As a result, age at onset and motor and non-motor features of LRRK2-PD patients were similar to IPD patients except for milder non-motor symptoms. In contrast, GBA-PD patients had a significantly younger age at onset and higher Unified Parkinson's Disease Rating Scale scores than LRRK2-PD and IPD patients. In addition, postural instability and gait disorders, motor complications, cognitive decline, hallucination, sexual dysfunction, and constipation were more frequent in GBA-PD than in LRRK2-PD and IPD patients, and GBA-PD patients had a worse performance for social functioning and role-emotional scores. Our study represents the first large-scale clinical study of LRRK2-PD and GBA-PD in ethnic Chinese individuals. The data suggest that both LRRK2-PD and GBA-PD are similar to IPD, except for an earlier age at onset and relatively more common non-motor symptoms in GBA-PD patients. These findings strengthen our understanding of the clinical heterogeneity of PD, and may have implications for molecular classification of the disease.

Keywords: Clinical profiles; GBA; Genetic variant; LRRK2; Parkinson's disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age of Onset
  • Aged
  • Asian People
  • Cell Adhesion Molecules, Neuronal / genetics*
  • Cognition
  • Constipation
  • Emotions
  • Female
  • Gait
  • Glucosylceramidase / genetics*
  • Humans
  • Male
  • Middle Aged
  • Motor Activity
  • Mutation*
  • Parkinson Disease / genetics*
  • Parkinson Disease / physiopathology
  • Parkinson Disease / psychology
  • Posture
  • Sexual Dysfunction, Physiological
  • Social Behavior

Substances

  • Cell Adhesion Molecules, Neuronal
  • LRRN2 protein, human
  • Glucosylceramidase