帕金森氏症(Parkinson's disease；簡稱PD)是一種漸進式、與年齡相關的神經退化性疾病。臨床上典型的症狀為在中腦黑質緻密區會有多巴胺神經元的大量死亡，並伴隨出現路易體(Lewy Body)。在病人身上會有顫抖、僵直、行動遲緩等症狀。研究到目前為止，真正導致PD的病理機制尚不明確，但文獻傾向於認為是由於基因和環境因子共同影響而造成PD的發病。目前已知的PD相關基因包含α-synuclein、parkin、ubiquitin carboxy-terminal hydrolase、DJ-1、PINK1、LRRK2等，其中parkin和DJ-1與體染色體隱性遺傳帕金森氏症相關，此類PD不同於典型PD，具有早發性以及病理上無路易體的特徵。本研究分析台灣族群帕金森氏症患者在parkin與DJ-1基因的變異。parkin cDNA定序結果發現有兩個缺失突變(Δ138Ala和Δexon5)和兩個報導過的多型性點(S167N與V380L)，另外也有七個新發現的點突變。DJ-1基因的部份，並沒有發現有任何與文獻上相符合的突變點，只在DJ-1基因外顯子四發現一同型合子的靜默突變點（G78G）。另一方面，基於粒線體功能缺失一直被認為與帕金森氏症（Parkinson's disease）的致病相關。本研究針對416個病人與372位性別、年齡相當的正常人進行粒線體基因多型性點（9055G/A、10398G/A、13708G/A）的分析（case-control study）。統計結果顯示此三個基因多型性點出現頻率在正常人與病人族群中未達顯著差異；另外在性別與haplotype的分布也沒有顯著差異。然而，在大於七十歲以上的次族群中發現，haplotype 9055G-10398A-13708G在統計上達顯著差異。本研究結果顯示粒線體DNA haplotype 9055G-10398A-13708G的分布可能在台灣七十歲以上的帕金森氏症族群中扮演增加疾病感受性的角色。

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

王政光. 人類遺傳疾病第一部份：台灣帕金森氏症的分子遺傳研究. 國立台灣師範大學生命科學系九十三學年度博士論文, 2005.
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