請用此 Handle URI 來引用此文件:
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/37263
標題: | 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 Associations of Genetic Polymorphisms with Lipid Lowering Effects of Statin Therapy |
作者: | Chen-Hsu Lo 羅振旭 |
指導教授: | 陳燕惠(Yen-Hui Chen) |
關鍵字: | atorvastatin,rosuvastatin,史達汀,單核甘變異性,基因多型性,膽固醇, atorvastatin,rosuvastatin,HMG-CoA reductase inhibitor,single nucleotide polymorphism,cholesterol, |
出版年 : | 2008 |
學位: | 碩士 |
摘要: | 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。 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. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/37263 |
全文授權: | 有償授權 |
顯示於系所單位: | 臨床藥學研究所 |
文件中的檔案:
檔案 | 大小 | 格式 | |
---|---|---|---|
ntu-97-1.pdf 目前未授權公開取用 | 1.62 MB | Adobe PDF |
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。