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

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. (c) 2022 International Parkinson and Movement Disorder Society.