Identification of a common genetic risk variant (LRRK2 Gly2385Arg) in Parkinson's disease

ABSTRACT

The recent identification of a common genetic variant (LRRK2 G2385R) which is associated with a two-fold increased risk of sporadic Parkinson's Disease (PD) in two independent Chinese populations in Singapore and Taiwan has generated considerable excitement. Thus far, this variant appears specific for the Asian population, emphasising further that ethnic-specific effects should be considered in genetic association studies. Cautious optimism is advised as we await more scientific studies and clarification if this risk variant is specific to ethnic Chinese race. Our in-vitro studies suggest the Gly2385Arg variant is biologically relevant and it might act through pro-apoptotic mechanisms, especially under cellular stresses. This may provide a partial explanation why some carriers develop the disease while others do not. The presence of other epigenetic factors, gene-gene and gene-environmental interaction could modulate the phenotype expression. Further validation of these findings would be needed to confirm this variant as the single most important common genetic risk factor in ethnic Chinese and/or Asian PD patients. The identification of the LRRK2 Gly2385Arg variant could potentially facilitate the development of clinical, bioimaging, genetic and biological biomarkers, useful in the monitoring and neuroprotective therapy in asymptomatic individuals.