Molecular genetic studies of parkin, DJ-1 gene mutations and mitochondrial DNA polymorphisms in Taiwanese Parkinson’s disease

• Main Author: 管郡潔
• Other Authors: 李桂楨
• Format: Others
• Language: zh-TW
• Published: 2007
• Online Access: http://ndltd.ncl.edu.tw/handle/01754818143608542341

碩士 === 國立臺灣師範大學 === 生命科學研究所 === 95 === Parkinson’s disease (PD) is the second most common neurodegenerative disorder characterized by resting tremor, rigidity, bradykinesia, and postural instability. Besides, the pathological features are the presence of intraneural inclusions, Lewy bodies, and selected loss of neurons in the substantia nigra. Based on previous studies, parkin nad DJ-1gene involved in autosomal recessive juvenile parkinsonism (AR-JP), which characterized by early onset and pathology demonstrated loss of the neurons in substantia nigra but absence of Lewy body. On the other hand, it has been suggested that mitochondrial dysfunction could be involved in PD, and several mitochondrial single-nucleotide polymorphism (SNP) have been reported. Therefore, we detect parkin and DJ-1 mutions in Taiwanese population. Direct sequencing of the parkin and DJ-1 gene found two deletion(Δ138Ala and Δexon5), two reported SNP and seven novel point mutation. We also analyzed whether these three genetic polymorphisms are associated with PD in a cohort of 416 PD cases and 372 ethnically matched controls. The allele frequency distribution of any of these three analyzed polymorphisms was not significantly different between the cases and the controls. None of the six haplotypes derived influences risk of PD. Notably, after stratification by age, individuals over 70 years of age carrying the haplotype 9055G-10398A-13708G demonstrated a significant decrease in risk of developing PD (OR = 0.44, 95% CI = 0.24-0.80, p = 0.008). These results suggest that the mtDNA haplotype 9055G-10398A-13708G plays a role in PD susceptibility among Taiwanese people older than 70 years of age