LRRK2基因，全名為leucine-rich repeat kinase 2 (轉譯出LRRK2蛋白，又稱震顫素)，是目前引起體染色體顯性遺傳的帕金森氏症的重要基因。LRRK2蛋白在體內各處皆有表現，包括中央神經系統、主要器官及淋巴球等。先前我們針對早發型帕金森氏症患者進行LRRK2 cDNA定序，找到兩個未被報導過的R767H與S885N突變，及六個改變胺基酸的多型性。本研究進一步探究LRRK2與台灣帕金森氏症的相關性。結果於21位早發性PD患者的cDNA定序發現一個未改變胺基酸的變異N2047 T>C。PCR-RFLP檢測PD患者的已知突變亦新發現一S885N突變。帕金森氏症患者的病例-對照組研究結果顯示，G2385R的GA基因型及A等位基因與帕金森氏症顯著相關。另外，本研究亦建構EGFP及Myc-His標記的野生型及R767H、S885N突變型的LRRK2質體，送到HEK-293T細胞中表現，西方轉漬分析、螢光顯微鏡觀察、活細胞影像儀觀察結果顯示，野生型LRRK2-EGFP融合蛋白主要分佈在細胞質，且與粒線體及內質網等胞器位置重疊，突變型的LRRK2蛋白在細胞中的表現情況與野生型相似，並無明顯差異。

　　Mutations in leucine-rich repeat kinase 2 (LRRK2, encoding dardarin) is the most common cause of autosomal dominant PD. LRRK2 protein is expressed ubiquitously, particularly in the central nervous system, major organs and also in the lymphocytes. Previously we screened LRRK2 mutations in early-onset PD (EOPD) patients and identified two novel (R767H and S885N) mutations, in addition to 6 nonsynonymous amino acid substitutions. In this study, 21 newly recruited EOPD patients were screened using direct cDNA sequencing and one novel N2047 T>C variant was identified. PCR-RFLP analysis of the known mutation also identified a S885N mutation carrier. In addition, the results of a case-control study in a cohort of PD and ethnically matched controls revealed that G2385R GA genotype or A allele was significantly associated with the risk of PD. Finally, the EGFP- and Myc-tagged wild type, R767H and S885N LRRK2 constructs were transiently expressed in HEK-293T cells. Western blot analysis and immunofluorescence microscopy examination revealed that both wild type and mutant LRRK2 proteins exhibit similar cytoplasmic distribution and mitochondria and endoplasmic reticulum co-localization.

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