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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 陳燕惠(Yen-Hui Chen) | |
dc.contributor.author | Chen-Hsu Lo | en |
dc.contributor.author | 羅振旭 | zh_TW |
dc.date.accessioned | 2021-06-13T15:22:49Z | - |
dc.date.available | 2010-08-08 | |
dc.date.copyright | 2008-08-08 | |
dc.date.issued | 2008 | |
dc.date.submitted | 2008-07-23 | |
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/37263 | - |
dc.description.abstract | 史達汀(statins)為3-hydroxy-3-methylglutaryl-coenzyme A還原脢抑制劑。史達汀的療效在個體間存在廣大差異,基因多型性為可能原因之一。目前已有一些研究探討與脂質合成或代謝相關的基因,其變異性對史達汀療效的影響。但這些研究大多著重於高加索人種,對於亞洲人種相關基因的單核甘酸多型性與史達汀療效的相關性仍然沒有足夠的資料。本研究將探討史達汀如atorvastatin(ATV)與rosuvastain(RSV)對血脂值的影響與病患基因型的相關性。
本研究收集使用ATV或RSV連續4週以上,且在開始治療前與4週後有完整血脂檢驗值的病患共132人,然後利用病患的DNA進行基因型測定,包括在血脂生成、代謝有關的基因,如ABCA1、ABCG2、ABCG5/G8、FDFT1、HMGCR、LDLR和CETP;與藥物代謝有關的基因,如CYP2C9/19、CYP3A4/5、ABCB1、SLCO1B1等,總共48個SNPs,並探討這些SNPs與史達汀治療後的TG、TC、HDL膽固醇、LDL膽固醇濃度、非HDL膽固醇濃度、TG/HDL和TC/HDL之變化量的相關性。 在服用ATV的病患當中,在rs5929(LDLR,synonymous)為TT/TC基因型者有比CC基因型者更高的LDL膽固醇濃度降低量(-68.42±19.57 mg/dL比-57.64±21.85 mg/dL,p=0.029);而在服用RSV的病患當中,在rs4508523(LDLR,intron)為CC/TC基因型者有比TT基因型者更高的TC濃度降低量(-93.45±31.97 mg/dL比-62.17±48.15 mg/dL,p=0.035)、更高的TC/HDL比值降低量(-1.83±0.66比-1.14±1.00,p=0.029)和更高的NHDL膽固醇濃度降低量(-90.78±29.08 mg/dL比-59.67±46.91 mg/dL,p=0.025)。其它尚有與血脂值改變量顯著相關的SNPs,但以治療前血脂值校正之後即未達顯著水準。 本研究顯示在LDLR的基因變異性可能影響ATV或RSV的降脂效果。相符的結果是否能在更廣大的台灣地區族群中被觀察到仍須要進一步的研究。 | zh_TW |
dc.description.abstract | The 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, also known as statins, play an important role in the management of hypercholesterolemia and reduction of cardiovascular risks. It has been shown that genetic polymorphisms may contribute to variations of the response to statin therapy. However, most study population comprised Caucasians or African-Americans and the data obtained from Asians are scarce. This study aims to evaluate the association between genetic polymorphisms and atorvastatin (ATV), rosuvastatin (RSV) as well, among Asians in Taiwan.
The DNA of 132 hypercholestemic individuals treated with ATV 10 mg/day or RSV 10 mg/day were analyzed for 48 SNPs within genes related to lipid metabolism, including ABCA1、ABCG2、ABCG5/G8、FDFT1、HMGCR、LDLR、CETP and genes related to drug disposition, including CYP2C9/19、CYP2D6、CYP3A4/5、ABCB1、SLCO1B1. The variations in genetic polymorphisms were further examined for associations with changes of levels of triglycerides (TG), total cholesterol (TC), high density lipoprotein (HDL) cholesterol, non-HDL cholesterol and low density lipoprotein (LDL) cholesterol, and with the ratio of TG/HDL and TC/HDL. SNP site rs5929 and rs4508523 in gene coding for LDLR were significantly associated to the variation of ATV and RSV therapy, respectively. Among those treated with ATV, individuals with more than one copy of T allele at rs5929 in LDLR had greater reduction in LDL cholesterol level (-68.42±19.57 mg/dL vs -57.64±21.85 mg/dL, p=0.029). Within those treated with RSV, individuals with more than one copy of C allele had greater reduction in level of TC (-93.45±31.97 mg/dL vs -62.17±48.15 mg/dL, p=0.035), TC/HDL (-1.83±0.66 vs-1.14±1.00, p=0.029), and non-HDL cholesterol (-90.78±29.08 mg/dL vs -59.67±46.91 mg/dL, p=0.025). Several SNPs were found to be related to the reduction of lipid levels, but the associations were no longer statistically significant after correction with baseline lipid levels. This study concluded that genetic polymorphisms in LDLR may affect the response of ATV and RSV. Results of this study need to be further validated in a larger, independent and prospective study. | en |
dc.description.provenance | Made available in DSpace on 2021-06-13T15:22:49Z (GMT). No. of bitstreams: 1 ntu-97-R94451007-1.pdf: 1654550 bytes, checksum: e81d829e7ec5fd36d7bc93294d1f7ddf (MD5) Previous issue date: 2008 | en |
dc.description.tableofcontents | 中文摘要 i
英文摘要 iii 目錄 v 表目錄 vii 圖目錄 viii 中英對照表 ix 縮寫對照表 x 第1章 前言 12 1.1 文獻回顧 12 1.1.1 人體中脂質與脂蛋白代謝概述 12 1.1.2 動脈粥狀硬化形成的機制 13 1.1.3 高血脂症的治療原則 15 1.1.4 史達汀的作用機轉與臨床地位 17 1.1.5 史達汀的藥物基因體學 19 1.2 研究目的 26 第2章 材料與方法 27 2.1 研究族群 27 2.2 研究設計 27 2.3 檢體收集與處理方法 29 2.3.1 血液樣本處理 29 2.3.2 去氧核糖核酸檢體萃取 29 2.4 單核甘酸多型性的選擇與基因型鑑定 31 2.5 統計分析 32 第3章 研究結果 33 3.1 研究族群的基本特徵 33 3.2 ATV和RSV的降脂效果 33 3.3 基因多型性 34 3.4 ATV和RSV的降脂效果與基因多型性的相關性 35 第4章 討論 38 第5章 研究限制 43 第6章 結論 45 參考文獻 77 | |
dc.language.iso | zh-TW | |
dc.title | 基因多型性在高膽固醇血症的分佈及對於史達汀降脂效果的影響 | zh_TW |
dc.title | Associations of Genetic Polymorphisms with Lipid Lowering Effects of Statin Therapy | en |
dc.type | Thesis | |
dc.date.schoolyear | 96-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 陳為堅,王宗道(Tzung-Dau Wang) | |
dc.subject.keyword | atorvastatin,rosuvastatin,史達汀,單核甘變異性,基因多型性,膽固醇, | zh_TW |
dc.subject.keyword | atorvastatin,rosuvastatin,HMG-CoA reductase inhibitor,single nucleotide polymorphism,cholesterol, | en |
dc.relation.page | 86 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2008-07-23 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 臨床藥學研究所 | zh_TW |
顯示於系所單位: | 臨床藥學研究所 |
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