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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
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dc.contributor.advisor | 賴凌平(Ling-Ping Lai) | |
dc.contributor.author | Yi-Jung Chen | en |
dc.contributor.author | 陳怡蓉 | zh_TW |
dc.date.accessioned | 2021-06-13T07:12:16Z | - |
dc.date.available | 2007-08-12 | |
dc.date.copyright | 2005-08-12 | |
dc.date.issued | 2005 | |
dc.date.submitted | 2005-07-26 | |
dc.identifier.citation | Ausma J, Wijffels M, Thone F, Wouters L, Allessie M, Borgers M (1997) Structural changes of atrial myocardium due to sustained atrial fibrillation in the goat. Circulation. 96(9): 3157–3163.
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/35827 | - |
dc.description.abstract | 背景
心房顫動(Atrial Fibrillation, AF)屬於最常見的心律不整, 常伴隨有心悸、胸痛、頭暈的症狀,且容易引起中風、心臟衰竭,及引發死亡的危險。曾有研究顯示,心房顫動與先天遺傳因素相關,而由於心臟細胞中構成間隙連接的分子,connexin40 與心肌間的電氣傳導有關,因此我們探討connexin40 的基因多型性與心房顫動間的關係。 病患與方法 本實驗主要研究connexin40(Cx40 -44G>A 與Cx40 71A>G)的單一 核苷酸多型性與心房顫動的關聯性。我們收集了173 位平均年齡為 69.6±12.6 的心房顫動病人,並收集無心房顫動的對照組進行分析。此外,並利用repoter assay,觀察轉殖有Cx40(-44G,+71A)與Cx40(-44A,+71G)兩種不同單一核苷酸多型性之HL-1 細胞其luciferase蛋白表現的差異。 結果 我們發現connexin40 上的兩個單一核苷酸多型性Cx40 -44G>A與Cx40 +71A>G 都和與心房顫動有顯著的相關。單套體分析結果顯 示,Cx40 上的兩個單一核苷酸多型性呈現完全連鎖的狀態。在核苷 酸出現頻率的分析中,我們發現在病人的族群中,Cx40(-44A,+71G) 的出現機會明顯高於對照組(p=0.006, OR=1.514, 95% 信賴區間為 1.13~2.04);在基因型的分析上,發現這兩個單一核苷酸多型性傾向以隱性模式產生影響(p=0.004, OR=2.713, 95% 信賴區間為 1.34~5.50)。最後在Cx40 多型性的功能分析上,我們利用觀察 luciferase 蛋白的表現變化,發現Cx40(-44A,+71G)相較於Cx40 (-44G,+71A)其luciferase 的表現有明顯的減少。 結論 Connexin40 上的兩個單一核苷酸多型性Cx40 -44G>A 與Cx40 +71A>G 確實與心房顫動相關,其中Cx40(-44A+71G)會伴隨有較高的 心房顫動的風險。而在啟動子能力分析中,我們發現Cx40 啟動子上 的兩個核苷酸多型性對luciferase 的表現有顯著的影響。 | zh_TW |
dc.description.abstract | Background
Atrial Fibrillation is the most commonly encountered arrhythmia and is frequently accompanied with many morbidities and mortalities. There is evidence showing that genetic factors contribute to the pathogenesis of atrial fibrillation. In the present study, we investigated the relationship between atrial fibrillation and polymorphism of the connexin40 gene, which is important in the coupling between atrial myocytes. Patients and Methods We performed an association study between two of connexin40 single nucleotide polymorphisms (SNPs) (CX40 -44G>A and CX40 71A>G) and atrial fibrillation. We enrolled 173 patients with atrial fibrillation patients and the control group patients without atrial fibrillation. The luciferase assay was performed to evaluate the promoter activities of two different Cx40 genotypes in HL-1 cell. Results We found that the two SNPs were both significantly associated with atrial fibrillation. In haplotype analysis, Cx40 -44G was always associated with Cx+71A while Cx-44A with Cx40+71G. Therefore, the two SNPs were completely linked. In the analysis of allele frequency, we demonstrated that the incidence of Cx40 (-44A, +71G) was significantly higher in the patient group than in the control group (p=0.006, OR=1.514, 95% CI 1.13~2.04). In the function assay of Cx40 polymorphisms, we examined the alteration of luciferase protein expression, and concluded that the rare genotype Cx40(-44A, +71G) was significantly lower in Cx40 promoter activity. Conclusion The two single nucleotide polymorphisms of connexin40, CX40 -44G>A and CX40 +71A>G, were significantly associated with atrial fibrillation. The Cx40 (-44A,+71G) haplotype had a higher risk for developing atrial fibrillation. Yet the two polymorphisms in Cx40 promoter did differ significantly in luciferase activity when expressed in HL-1 cells. | en |
dc.description.provenance | Made available in DSpace on 2021-06-13T07:12:16Z (GMT). No. of bitstreams: 1 ntu-94-R92443008-1.pdf: 2130846 bytes, checksum: 74786a6e59e15eab09399be5bfd1a9cc (MD5) Previous issue date: 2005 | en |
dc.description.tableofcontents | 縮寫表(Abbreviations) ………………………………………… 0
中文摘要(Abstract in Chinese)………………………………… 1 英文摘要(Abstract in English) ……………………………… 3 序論(Introduction) ……………………………………………… 5 圖一:心臟電氣傳導系統………………………………………… 6 圖二:心房顫動的心電圖………………………………………… 7 圖三:心房纖維顫動的分類表…………………………………… 7 表一:引起心房纖維顫動的原因………………………………… 8 圖四:心房顫動的三種電氣機轉………………………………… 9 圖五:心房重塑的正回饋關係圖………………………………… 10 圖六:心房顫動電氣重塑的離子電流的改變…………………… 12 表二:治療心律不整藥物的分類………………………………… 13 圖七:間隙連接示意圖…………………………………………… 17 表三:常見的單一核苷酸多型性檢測方式……………………… 20 材料與方法(Materials and Methods) ………………………… 22 表四:基因變異的資料來源……………………………………… 23 表五;實驗中所用的引子以及聚合酶連鎖反應的反應條件…… 25 表六:聚合酵素連鎖反應地添加物及濃度……………………… 26 表七:單一核苷酸多型性所使用的限制酶及電泳模式………… 27 結果(Results)………………………………………………………31 表八:病人與對照組的基本資料………………………………… 31 圖八:Cx40 -44G>A 的限制酶片段長度多型性電泳模式圖…… 32 圖九:Cx40 71A>G 的限制酶片段長度多型性電泳模式圖………33 表九:Cx40 -44G>A 及Cx40 71A>G 的基因分析結果……………35 表十:Cx40 -44G>A 及Cx40 71A>G 的基因多變數分析結果……36 圖十:帶有Cx40 -44G,+71A 與Cx40 -44A,+71G 兩種不同基因 型的HL-1 細胞之luciferase 檢測結果………………………… 37 圖十一:angiotensinⅡ對Cx40(-44G,+71A)與Cx40(-44A,+71G) 兩種不同基因型的HL-1 細胞之luciferase 表現之檢測結果… 38 討論(Discussion)………………………………………………… 39 圖十二:Cx40 啟動子基因變異與其表現的比較圖………………42 結論與展望(Conclusion and Prospectives)…………………45 參考文獻(Reference) …………………………………………… 46 | |
dc.language.iso | zh-TW | |
dc.title | Connexin40 基因多型性與心房顫動之關聯研究 | zh_TW |
dc.title | Association Study on Connexin40 Genetic Polymorphism and Atrial Fibrillation | en |
dc.type | Thesis | |
dc.date.schoolyear | 93-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 林俊立,蘇銘嘉,楊偉勛 | |
dc.subject.keyword | connexin40,基因多型性,心房顫動, | zh_TW |
dc.subject.keyword | Connexin40,Polymorphism,Atrial Fibrillation, | en |
dc.relation.page | 53 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2005-07-27 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 藥理學研究所 | zh_TW |
顯示於系所單位: | 藥理學科所 |
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