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.
The Parkinson Disease and Movement Disorders Clinic, Sagol Neuroscience Center and Department of Neurology, Tel Aviv University, Israel.
Gilad
G
Yahalom
Natalie
N
Kaplan
Aya
A
Vituri
Oren S
OS
Cohen
Rivka
R
Inzelberg
Evgenia
E
Kozlova
Amos D
AD
Korczyn
Saharon
S
Rosset
Eitan
E
Friedman
Sharon
S
Hassin-Baer
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004252:DNA Mutational Analysis; D004409:Dyskinesia, Drug-Induced / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005998:Glycine / Q000235:genetics*; D006801:Humans; D007557:Israel; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D007980:Levodopa / Q000009:adverse effects; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010300:Parkinson Disease / Q000188:drug therapy / Q000453:epidemiology*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012189:Retrospective Studies; D012694:Serine / Q000235:genetics*; D018709:Statistics, Nonparametric; D055815:Young Adult
D012694:Serine; D007980:Levodopa; C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases; D005998:Glycine