LRRK2 G2385R and LRRK2 R1628P increase risk of Parkinson's disease in a Han Chinese population from Southern Mainland China

摘要

Parkinson's disease (PD) is one of the commonest neurodegener-ative diseases characterized by resting tremor, rigidity, bradykinesia, and postural instability. Mutations in the leucine-rich repeat kinase 2 (LRRK2) have been reported as the most frequent cause of familial autosomal dominant PD. However, there are variations in the prevalence of LRRK2 substitutions among different populations. For example, LRRK2 G2019S are most frequently identified in the United States, Europe, the Middle East, and North Africa, while LRRK2 G2385R and R1628P mutations are the most common genetic alterations in Asia. Recently, LRRK2 A419V, a new risk variant for PD, has been reported to increase the risk of PD with an odd's ratio over 7. However, subsequent studies revealed a remarkable difference in the frequency of LRRK2 A419V among different Han Chinese populations. LRRK2 A419V was found at a high frequency (3.0%) among Han Chinese from West China (P = 0.003; OR = 4.14) but very low frequency (~0.4%) among those from Southern China, Singapore and Taiwan [4], suggesting that some LRRK2 variants may be specific to a subset of Chinese Han population. Indeed, as the result of the immigration and assimilation of various regional ethnicities and tribes over the last thousand years, the Han Chinese population now has considerable genetic diversity. It has been reported that there is a north-south division in genetic variation within China. Although p.G2385R and p.R1628P have been investigated in different Chinese Han populations, there is little information about the frequency of those two LRRK2 variants in Southern China. Therefore, we examined the frequency of p.G2385R and p.R1628P in a Han Chinese population from Guangdong which is a Chinese province in the far south, to investigate the potential genetic heterogeneity for these two variants among different Han Chinese populations.