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標題: | 應用核磁共振氫譜技術探討台灣女性代謝體特徵與低骨質密度之關聯研究 Association of Metabolome with Low Bone Mineral Density in Taiwanese Women Revealed by 1H NMR Spectroscopy |
作者: | Ying-Shu You 尤瀅淑 |
指導教授: | 程蘊菁(Yen-Ching Chen) |
共同指導教授: | 林靖愉(Ching-Yu Lin) |
關鍵字: | 代謝體特徵,代謝體學,核磁共振氫譜,骨質疏鬆症,停經,女性, metabolomem,metabolic profiles,metabolomics,metabonomics,nuclear magnetic resonance,NMR,bone mineral density,osteoporosis,menopause,women, |
出版年 : | 2012 |
學位: | 碩士 |
摘要: | 背景:近期已有研究指出骨質疏鬆症與體內不斷循環的特定代謝物具有相關;然
而,若單靠過去研究所探討的少數幾項代謝物,很難對此複雜的致病機轉做詳確 的解釋。如今,代謝體學方法可全面性的檢視人體中代謝情形和潛在的臨床意義。 截至目前為止,未有研究加以驗證人體中代謝體特徵和骨質密度之間的相關。 方法:本研究橫斷式研究設計,自 2009 到 2010 年間招募 610 位年齡介於 40 至55 歲之間在台北美兆健康檢查中心參加健康檢查的台灣女性。使用雙能量放射線儀測量隻腰椎骨質密度,以骨質密度值的高低排序後研究族群依人數均分為三等份,定義骨質密度最高的第二和第三分群為「高骨質密度」組別,而最低的第 一群為「低骨質密度」組別。而血漿代謝體特徵資料是透過核磁共振氫譜實驗分 析所收集而成。運用無監督的主成分分析、監督的偏最小二乘法判別分析法及邏 輯斯迴歸模式,來分析代謝體特徵與骨質密度的相關。 結果:研究結果顯示,無監督的主成分分析的分數散佈圖無法完善地分離高低骨 質密度的組別;監督的偏最小二乘法判別分析法亦沒有能力區別高低骨質密度的 組別。根據停經狀態加以分層之後,可透過偏最小二乘法判別分析法於停經婦女 群體觀察到其代謝體特徵與高低骨質密度顯著的差異(R2= 0.12;Q2=0.04; P permutation =0.03)。此外,在停經婦女身上,會隨著glutamine的濃度升高,使得低骨質密度的風險增加;同時,低骨質密度也與lactate、acetone、lipid 和 very low density lipoprotein濃度降低具有相關。 結論:這是第一篇研究透過核磁共振氫譜實驗所建立的代謝體學與骨質密度之 研究,我們成功地於停經婦女群體辨識出一群代謝物和低骨質密度具有關聯。其 中,特別是glutamine的濃度升高會增加低骨質密度發生的風險,可能會因此導致骨骼流失。 Background. Osteoporosis has been related to the alteration of specific circulating metabolites previously. However, studies with few metabolites may have difficulty to explain the pathogenesis of this complex syndrome. Metabolome provide an overview of the metabolism status in human body and potential clinical implication. Up to date,no study has investigated the association between metabolome and bone mineral density (BMD). Methods. This is a cross-sectional study. A total of 610 healthy Taiwanese women aged 40 to 55 were recruited from MJ Health Screening Center between 2009 and 2010. High and low bone mineral density (BMD) was defined as the 2nd plus 3rd tertiles and the 1st tertile of BMD, respectively. The plasma metabolome were evaluated by 1H-nuclear magnetic resonance spectroscopy. Principal components analysis (PCA), partial least-squares discriminant analysis (PLS-DA), and logistic regression model were used to assess the association between metabolomeand BMD. Results. The unsupervised PCA showed no visual separation between low and high BMD levels; the supervised PLS-DA model was also unable to distinguish high and low BMD groups. After stratification by menopausal status, high and low BMD groups can be differentiated in post-menopausal women using PLS-DA (R2= 0.12;Q2=0.04; P permutation =0.03). In addition, elevated level of glutamine was associated with the risk of low BMD among postmenopausal women; while low BMD is characterized by decreased levels of lactate,acetone, lipid, and very low density lipoprotein in the same sub-population. Conclusion. This is the first study using 1H NMR-based metabolomic approach and successfully identified a group of metabolites representative for postmenopausal women with low BMD. Especially, elevated level of glutamine may lead to bone loss via increased risk of low BMD. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/6515 |
全文授權: | 同意授權(全球公開) |
顯示於系所單位: | 流行病學與預防醫學研究所 |
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