Correlation of tau gene polymorphism with age at onset of Parkinson's disease

Parkinson's disease (PD) is a neurodegenerative disease and its prevalence increases with age. The microtubule-associated protein tau (MAPT) is thought to be implicated in the pathogenesis of PD. Association of the MAPT H1 haplotype with PD in Caucasians has been extensively studied, however, the results were inconsistent. In this study, we investigated whether MAPT gene variants contribute to the pathogenesis process including the age at onset in Japanese PD. Promoter region of MAPT gene was analyzed to find polymorphisms in Japanese population. Two single nucleotide polymorphisms (SNPs), C-639T and Del-568TIns, in promoter region were found. C-639T was novel. Unlike Caucasians, the -226C and -45A alleles consisting of the H1 haplotype were monomorphic in Japanese population. Association analysis was performed using 240 PD and 191 controls in these SNPs. No significant association was observed between these SNPs and PD. Haplotype analysis also showed no significant association (P=0.72). However, the age at onset showed significant correlation with the genotypes of Del-568TIns in PD samples when analyzed by Kendall rank correlation test (Kendall tau=-0.098, P=0.0243). These results suggested that MAPT gene variants may modify the pathogenesis process of PD.