SNCA but not DNM3 and GAK modifies age at onset of LRRK2-related Parkinson's disease in Chinese population.

Abstract

Recently, rs2421947 in DNM3 (dynamin 3) was reported as a genetic modifier of age at onset (AAO) of LRRK2 G2019S-related Parkinson's disease (PD) in a genome-wide association study in Arab-Berber population. Rs356219 in SNCA (α-synuclein) was also reported to regulate the AAO of LRRK2-related PD in European populations, and GAK (Cyclin G-associated kinase) rs1524282 was reported to be associated with an increased PD risk with an interaction with SNCA rs356219. G2019S variant is rare in Asian populations, whereas two other Asian-specific LRRK2 variants, G2385R and R1628P, are more frequent with a twofold increased risk of PD. In this study, we investigated whether rs2421947, rs356219 and rs1524282 modified AAO in LRRK2-related PD patients in Han Chinese population. We screened LRRK2 G2385R and R1628P variants in 732 PD patients and 1992 healthy controls, and genotyped DNM3 rs2421947, SNCA rs356219 and GAK rs1524282 among the LRRK2 carriers. The SNCA rs356219-G allele was found to increase the risk of PD in LRRK2 carriers (OR 1.50, 95%CI 1.08-2.01, P = 0.016), and the AAO of AG + GG genotypes was 4years earlier than AA genotype (P = 0.006). Nonetheless, no similar association was found in DNM3 rs2421947 and GAK rs1524282. Our results show that SNCA but not DNM3 or GAK is associated with AAO of LRRK2-PD patients in Chinese population.