A 10-Year Community-Based Study of Leucine-Rich Repeat Kinase 2 G2385R Carriers' Conversion to Parkinson's Disease.

ABSTRACT

BACKGROUND: The G2385R variant of leucine-rich repeat kinase 2 (LRRK2) is mainly associated with Parkinson's disease(PD) in Asian populations. OBJECTIVE: The aim of this study was to investigate the PD conversion rate and clinical characteristics of LRRK2 G2385R nonmanifesting carriers. METHODS: All participants were from the community-based longitudinal cohort of Shanghai Ruijin Hospital. The G2385R carriers and noncarriers were screened by Sanger sequencing and received face-to-face interviews at baseline and follow-up assessments. The Kaplan-Meier method was used to compare the conversion rate of PD. Cox regression models were used to estimate the risk of G2385R variant for PD. RESULTS: In the combined cohort, 26 (7.9%) people developed PD in 329 carriers versus 9 (2.6%) in 345 noncarriers (P = 0.0016). Cox regression model confirmed that the G2385R variant was a strong risk factor for PD in a Chinese population older than 50 years (hazard ratio, 3.314; 95% confidence interval, 1.551-7.078; P = 0.002). No difference was found in clinical symptoms between carriers and noncarriers. CONCLUSIONS: We confirmed an increased conversion of PD in leucine-rich repeat kinase 2 G2385R carriers during a 10-year follow-up. © 2022 International Parkinson and Movement Disorder Society.