https://scholars.lib.ntu.edu.tw/handle/123456789/145817
標題: | 變異型脂蛋白元A5 185C之表現與血清脂蛋白元A5濃度及其基因變異的相關性 Expression of Apoiliprotein A5 Variant 185C and Association between Its Plasma Concentration and Genetic variation of Apolipoprotein A5 |
作者: | 林燕琳 lin, Yen-Lin |
關鍵字: | 變異型脂蛋白元A5 185C;基因變異;脂蛋白元A5;Apolipoprotein A5 variant 185C;Genetic variation;APOA5;APOA5 SNP;APOA5 185C;Apolipoprotein A5 | 公開日期: | 2004 | 摘要: | 高三酸甘油酯血症是一種相當常見、致因多樣化的代謝性異常疾病,因製造過多、或無法有效清除血液中富含三酸甘油酯的脂蛋白所導致,且高三酸甘油酯血症亦為罹患心血管疾病的重要危險因子之一。 血液中的脂質是由脂蛋白所攜帶以進行代謝;同時,在脂蛋白上含有各式各樣的脂蛋白元,這些脂蛋白元有其不同的功能並調節著脂質及脂蛋白的清除。脂蛋白元A5為近年新發現的一個脂蛋白元,根據最早的研究指出,在脂蛋白元A5的基因轉殖小鼠中,其血液三酸甘油酯的濃度大輻下降,相反的,在脂蛋白元A5基因剔除的小鼠中,三酸甘油酯濃度則明顯上升;此外,當小鼠血清中脂蛋白元A5的表現量增加時,三酸甘油酯濃度也隨之減低,而近期的研究則更確切指出,脂蛋白元A5可能透過促進脂蛋白解脂酶的水解能力,來達到降低血中三酸甘油酯的含量。 而在人類脂蛋白元A5基因的多型性研究中,顯示了許多SNPs與高三酸甘油酯血症具有統計學上的相關性。由本實驗室發現的MspI多型性,會造成脂蛋白元A5第185個胺基酸由甘胺酸(glycine)變異為半胱胺酸(cysteine)。為瞭解此變異型脂蛋白元A5影響三酸甘油酯正常代謝之因素,在本篇論文中,建構了此變異型之質體,以人類293細胞表現之。在與野生型脂蛋白元A5相較下,發現變異型脂蛋白元A5可能累積在細胞內,而無法分泌至細胞外,且其半生期也可能較野生型的短。 另外,在針對人類血清中脂蛋白元A5濃度之分析發現,HTG (hypertriglyceridemia)組之平均濃度較NTG (normolipidemic subjects)組高,且兩者之差異具有統計學上的意義。而將脂蛋白元A5之濃度與APOA5各個SNPs進行分析,發現在NTG組中,c.1259T>C 與 IVS3+467G>A多型性與血清中脂蛋白元A5濃度具有相關性。 Hypertriglyceridemia(HTG)is a common metabolic disorder resulted from multiple determinants. It may arise from either over-production or defective clearance of triglyceride-rich lipoproteins in circulation. Furthermore, HTG is also one of the risk factors involved in coronary heart diseases. Plasma lipid is known to be carried by lipoproteins and to undergo further hydrolysis. Meanwhile, diverse-functioned apolipoproteins on lipoproteins modulate clearance of lipid and lipoproteins. ApoAV was discovered as a new member of the apolipoprotein. Early studies indicated that the level of plasma triglyceride(TG) dropped dramatically in APOA5 transgenic mice when compared with wild type mice. In contrast, apoa5 knockout mice had much higher TG contents than wild type mice did. Besides, the concentration of apoA5 exerted a reverse correlation with that of TG in mice. Recently studies have obtained evidence that apoAV can activate the triacylglycerol hydrolase activity of LPL to reduce the plasma triglyceride. The studies also revealed that APOA5 gene polymorphism in human was statistically correlated with the incidence of HTG. We have identified the MspI polymorphism, resulting in the substitution of cysteine for glycine at residue 185. In order to find out the mechanism of the effect of APOA5 185C variant, we constructed the vector, which can express apoAV protein in HEK 293 cells. Through the analysis between wild type and variant, it was found that the apoAV variant may accumulate inside the cells and may not be secreted. We also analyzed the concentration of apoAV in plasma. The mean concentration of apoAV in HTG (hypertriglyceridemia) was higher than that in NTG (normolipidemic subjects) and the difference was statistically significant. In APOA5 SNPs, c.1259T>C and IVS3+467G>A polymorphisms were significantly associated with apoAV levels in NTG. |
URI: | http://ntur.lib.ntu.edu.tw//handle/246246/62845 | 其他識別: | zh-TW |
顯示於: | 醫學檢驗暨生物技術學系 |
檔案 | 描述 | 大小 | 格式 | |
---|---|---|---|---|
ntu-93-R91424014-1.pdf | 23.31 kB | Adobe PDF | 檢視/開啟 |
在 IR 系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。