Dyskinesias in patients with Parkinson's disease: effect of the leucine-rich repeat kinase 2 (LRRK2) G2019S mutation.


BACKGROUND While Parkinson's disease (PD) phenotype in leucine-rich repeat kinase 2 gene (LRRK2)-associated and sporadic PD seems similar, there is paucity of data on the possible effect of mutations in LRRK2 on response to and complications of dopaminergic therapy. OBJECTIVE To assess the impact of the LRRK2 Gly2019Ser (G2019S) carrier status on the time to the onset of levodopa-induced dyskinesias (LID). METHODS Consecutive PD patients treated with levodopa were genotyped for the LRRK2 G2019S mutation. The relationship between mutation carrier status and the time to LID onset was explored after matching carriers to non-carriers for age at PD onset, gender, and time from PD diagnosis to levodopa initiation, using Kaplan-Meier curves and the Cox proportional hazards model, using LID onset as an end-point. RESULTS Overall, 349 Israeli PD patients [222 Ashkenazi-Jewish (AJ), 60.5% males, mean age at diagnosis: 60.6 ± 13.2 years] participated in the study. Of these, 33 patients (9.5%, 30 AJ) carried the LRRK2 G2019S mutation. The prevalence of LID was non-significantly higher among carriers (22/33, 66.7%) than non-carriers (168/316, 53.2%, p = 0.15). The mean duration of therapy from levodopa initiation to the development of LID or last follow-up (in cases who were LID-free) was 5.1 ± 5.4 years for carriers and 4.4 ± 4.0 years in non-carriers (p = 0.47) and the survival curves in carriers and matched non-carriers were not significantly different (Cox proportional hazards test and log-rank test; p = 0.79). CONCLUSIONS The LRRK2 G2019S mutation status has no discernable effect on the prevalence of LID or on LID latency in Israeli levodopa-treated PD patients.

DOI: 10.1016/j.parkreldis.2012.05.014

Cite this paper

@article{Yahalom2012DyskinesiasIP, title={Dyskinesias in patients with Parkinson's disease: effect of the leucine-rich repeat kinase 2 (LRRK2) G2019S mutation.}, author={Gilad Yahalom and Natalie Kaplan and Aya Vituri and Oren S. Cohen and Rivka Inzelberg and E. Kozlova and Amos D. Korczyn and Saharon Rosset and Eitan Friedman and Sharon Hassin-Baer}, journal={Parkinsonism & related disorders}, year={2012}, volume={18 9}, pages={1039-41} }