SNCA gene, but not MAPT, influences onset age of Parkinson's disease in Chinese and Australians

Abstract

Background. α-Synuclein (SNCA) and microtubule-associated protein tau (MAPT) are the two major genes independently, but not jointly, associated with susceptibility for Parkinson's disease (PD). The SNCA gene has recently been identified as a major modifier of age of PD onset. Whether MAPT gene synergistically influences age of onset of PD is unknown. Objective. To investigate independent and joint effects of MAPT and SNCA on PD onset age. Methods. 412 patients with PD were recruited from the Australian PD Research Network (123) and the Neurology Department, Ruijin Hospital Affiliated to Shanghai Jiaotong University, China (289). MAPT (rs17650901) tagging H1/H2 haplotype and SNCA (Rep1) were genotyped in the Australian cohort, and MAPT (rs242557, rs3744456) and SNCA (rs11931074, rs894278) were genotyped in the Chinese cohort. SPSS regression analysis was used to test genetic effects on age at onset of PD in each cohort. Results. SNCA polymorphisms associated with the onset age of PD in both populations. MAPT polymorphisms did not enhance such association in either entire cohort. Conclusion. This study suggests that, in both ethnic groups, SNCA gene variants influence the age at onset of PD and α-synuclein plays a key role in the disease course of PD.