促發炎細胞激素啟動子多型性與台灣帕金森氏症感受性的相關性研究
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2006
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帕金森氏症(PD)是一種與年齡相關的神經退化性疾病。目前的相關研究認為帕金森式症成因可能是多種因素共同交互影響產生的結果，包括遺傳因素、環境因素及神經性發炎都可能影響帕金森氏症的發病進程。本研究分析台灣帕金森氏症患族群及正常人族群的IL-1β、IL-6和IL-8基因啟動子區域上的單一核苷酸位點之多型性(single nucleotide polymorphism; SNP)變異，比較正常人與帕金森氏症患者的IL-1β C-511T、IL-6 G-174C和IL-8 T-251A啟動子多型性的差異，以及其不同的基因型與帕金森患者開始發病年齡(age- at-onset)、性別的相關性分析，但並未發現此三種細胞激素與PD發病有相關性。另外選取帶有特定TNF-α -1031基因型(TT或CC)之帕金森患者的淋巴細胞株，以內毒素Lipopolysaccharide (LPS)誘發細胞發炎反應後，藉RT-PCR與同步定量PCR實驗方法，分析TNF-α mRNA表現量，發現各淋巴細胞株對於TNF-α的感受性也有差異。若以cytokine protein array的技術，在促使細胞發炎情況下檢視多種細胞激素的表現量，則發現PD病患之淋巴細胞株經LPS處理後，較正常人之淋巴細胞株釋放出更多的 thrombpoietin、EGF及TNF-β。
Parkinson's disease (PD) is a neurodegenerative disorder related with aging. The pathogenesis of sporadic PD is thought to be the result of interactions of multiple factors, including inherited factors, environmental factors and neuroinflammation. In the present study, single nucleotide polymorphisms (SNPs) of the promoter region of interleukin-1β gene (IL-1β, C-511T), interleukin-6 gene (IL-6, G-174C) and interleukin-8 gene (IL-8, T-251A) were evaluated for the association with the risk of Taiwanese PD in a case-control study using PCR-restriction enzyme assay. However, the overall genotype and allele distributions at these three sites showed no significant difference between PD cases and controls, even after stratification by age or sex. In addition, RT-PCR and real-time PCR quantitation of LPS-induced TNF-α production in two PD lymphoblastoid cells carrying the TNF-α -1031TT or CC genotype displayed differential expression. The cytokine protein array experiment further revealed that higher level of thrombpoietin, EGF and TNF-β might be induced in response to LPS stimulation in PD lymphoblastoid cells as compared to control lymphoblastoid cells.
Parkinson's disease (PD) is a neurodegenerative disorder related with aging. The pathogenesis of sporadic PD is thought to be the result of interactions of multiple factors, including inherited factors, environmental factors and neuroinflammation. In the present study, single nucleotide polymorphisms (SNPs) of the promoter region of interleukin-1β gene (IL-1β, C-511T), interleukin-6 gene (IL-6, G-174C) and interleukin-8 gene (IL-8, T-251A) were evaluated for the association with the risk of Taiwanese PD in a case-control study using PCR-restriction enzyme assay. However, the overall genotype and allele distributions at these three sites showed no significant difference between PD cases and controls, even after stratification by age or sex. In addition, RT-PCR and real-time PCR quantitation of LPS-induced TNF-α production in two PD lymphoblastoid cells carrying the TNF-α -1031TT or CC genotype displayed differential expression. The cytokine protein array experiment further revealed that higher level of thrombpoietin, EGF and TNF-β might be induced in response to LPS stimulation in PD lymphoblastoid cells as compared to control lymphoblastoid cells.
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帕金森氏症, 介白素-1, 介白素-6, 介白素-8, 促發炎細胞激素, Parkinson's disease, IL-1, IL-6, IL-8, proinflammatory cytokines, SNPs