Analysis of KLK1 Gene-130Gn Polymorphism with the Risk of Parkinson's Disease
No Thumbnail Available
Date
2005-06-??
Authors
黃淑宜
莊蕙瑄
陳瓊美
吳逸如
李桂楨
Journal Title
Journal ISSN
Volume Title
Publisher
國立臺灣師範大學生命科學學系
Department of Life Science, NTNU
Department of Life Science, NTNU
Abstract
帕金森氏症為一常見的神經退化性疾病，和遺傳及環境因素相關。KLK1為一serine protease，在人體包括大腦皮質、海馬迴等多處部位皆有表現。本研究的目的在探討KLK1基因啟動子-130G(下標 N)多型性與國人帕金森氏症感受性的相關性。-130G(下標 N)多型性基因型的分析方法包括螢光PCR產物的長度分析、單股核酸構形多型性／異雙股分析及DNA定序等。所研究樣品群包括208位帕金森氏症患者及95位正常人。結果共觀察到五種對偶基因：I (G9)、A (G10)、B (G2CG7)、H (G11)、K (Gl2)。多型性對偶基因的啟動子轉錄活性分析顯示，在人類胚胎腎細胞HEK-293及人類腦癌細胞IMR-32中，A、B、H對偶基因的轉錄活性並無顯著差異，但三者的轉錄活性均較K對偶基因顯著的好。進一步的依據含或不含K對偶基因的基因型，或K對偶基因頻率，進行X^2統計分析，結果顯示在正常人族群與帕金森氏症患者群間，並未呈現顯著差異。故推論KLK1基因啟動子多型性，雖然會影響其在人類胚胎腎細胞及腦癌細胞中的表現量，但其變異和國人帕金森氏症的感受性並沒有太大關連性。
Parkinson's disease (PD) is a common neurodegenerative disorder involving several genetic and environmental components. Human tissue kallikrein (KLK1) is a serine protease expressed in both the cerebral cortex and hippocampus. In this study v e investigated the association of KLK1 gene -130G(subscript N) polymorphism with the risk of Parkinson's disease. The -130G(subscript N) polymorphism as analyzed by electrophoresis of fluorescenced PCR products in sequencing gels. single-strand conformation polymorphism (SSCP)/heteroduplex analysis and DNA sequencing. Two hundred and eight patients with PD and 95 normal controls ere examined. Five alleles ere identified in the KLK1 promoter: I (G9), A (G10), B (G2CG7), H (G11), and K (G12). A reporter construct containing the K allele cloned into a luciferase reporter plasmid drove significantly lower transcriptional activity of KLK1 as compared with the A, B, and H alleles in both HEK-293 and IMR-32 cells. However, when the genotype and allele frequencies with or without K allele were analyzed, no statistically significant difference as observed between PD patients and controls. Therefore, the results indicate that although associated with lower transcriptional activity, KLK1 -130G(subscript N) K allele as not associated with the risk of Taiwanese PD.
Parkinson's disease (PD) is a common neurodegenerative disorder involving several genetic and environmental components. Human tissue kallikrein (KLK1) is a serine protease expressed in both the cerebral cortex and hippocampus. In this study v e investigated the association of KLK1 gene -130G(subscript N) polymorphism with the risk of Parkinson's disease. The -130G(subscript N) polymorphism as analyzed by electrophoresis of fluorescenced PCR products in sequencing gels. single-strand conformation polymorphism (SSCP)/heteroduplex analysis and DNA sequencing. Two hundred and eight patients with PD and 95 normal controls ere examined. Five alleles ere identified in the KLK1 promoter: I (G9), A (G10), B (G2CG7), H (G11), and K (G12). A reporter construct containing the K allele cloned into a luciferase reporter plasmid drove significantly lower transcriptional activity of KLK1 as compared with the A, B, and H alleles in both HEK-293 and IMR-32 cells. However, when the genotype and allele frequencies with or without K allele were analyzed, no statistically significant difference as observed between PD patients and controls. Therefore, the results indicate that although associated with lower transcriptional activity, KLK1 -130G(subscript N) K allele as not associated with the risk of Taiwanese PD.