Genetic analysis of LRRK2 A419V variant in ethnic Chinese

Abstract Mutations in the leucine-rich repeat kinase 2 gene ( LRRK2 ) are the most common causes of autosomal dominant and sporadic forms of Parkinson's disease (PD). The A419V variant has been suggested to be a potential risk variant but its role among Chinese is unclear. We genotyped LRRK2 A419V variant to investigate the association with risk of PD. A total of 1314 subjects comprising 729 patients with PD and 585 controls were genotyped. Twenty-two (3.0%) patients were heterozygous carriers for the A419V variant, and the frequency was higher compared with controls (0.7%, p = 0.003). The association was seen among the younger age group (early onset PD patients vs. controls: p = 0.0005), but was not significant among the older age group (late onset PD patients vs. controls: p = 0.17). We showed a significant association of LRRK2 A419V variant among early onset PD in the ethnic Han Chinese population but not among late onset PD. Further replication studies in additional Chinese and other Asian cohorts will be important to address its potential pathophysiologic role.