請用此 Handle URI 來引用此文件：
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/59512完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 李芳仁(Fang-Jen Lee) | |
| dc.contributor.author | Jiun-Yi Nong | en |
| dc.contributor.author | 農君怡 | zh_TW |
| dc.date.accessioned | 2021-06-16T09:26:10Z | - |
| dc.date.available | 2020-09-12 | |
| dc.date.copyright | 2017-09-12 | |
| dc.date.issued | 2017 | |
| dc.date.submitted | 2017-06-05 | |
| dc.identifier.citation | Reference
1. Smith DJ, Salmi M, Bono P, Hellman J, Leu T, Jalkanen S (1998) Cloning of vascular adhesion protein-1 reveals a novel multifunctional adhesionmolecule. J Exp Med 188:17–27 2. Bono P, Salmi M, Smith DJ, Jalkanen S (1998) Cloning and characterization of mouse vascular adhesion protein-1 reveals a novel molecule with enzymatic activity. J Immunol 160:5563–5571 3. Lyles GA (1996) Mammalian plasma and tissue-bound semicarbazide-sensitiveamine oxidases: biochemical, pharmacological and toxicological aspects. Int J Biochem Cell Biol 28:259–274 4. Mercader J, Iffiú-Soltesz Z, Brenachot X, Földi A, Dunkel P, Balogh B et al (2010) SSAO substrates exhibiting insulin-like effects in adipocytes as a promising treatment option for metabolic disorders. Future Med Chem 2:1735-1749 5. Solé M, Unzeta M (2011) Vascular cell lines expressing SSAO/VAP-1: a new experimental tool to study its involvement in vascular diseases. Biol Cell 103:543-557 6. Valente T, Solé M, Unzeta M (2008) SSAO/VAP-1 protein expression during mouse embryonic development. Dev Dyn 237:2585-2593 7. Repessé X, Moldes M, Muscat A, Vatier C, Chetrite G, Gille T et al (2015) Hypoxia inhibits semicarbazide-sensitive amine oxidase activity in adipocytes. Mol Cell Endocrinol 411:58-66 8. Sun P, Solé M, Unzeta M (2014) Involvement of SSAO/VAP-1 in oxygen-glucose deprivation-mediated damage using the endothelial hSSAO/VAP-1-expressing cells as experimental model of cerebral ischemia. Cerebrovasc Dis 37:171-180 9. Sallisalmi M, Tenhunen J, Yang R, Oksala N, Pettila V (2012) Vascular adhesion protein-1 and syndecan-1 in septic shock. Acta Anaesthesiol Scand 56:316-322 10. Li HY, Wei JN, Lin MS, Smith DJ, Vainio J, Lin CH et al (2009) Serum vascular adhesion protein-1 is increased in acute and chronic hyperglycemia. Clin Chim Acta 404:149-153 11. Maciorkowska D, Zbroch E, Malyszko J (2015) Circulating renalase, catecholamines, and vascular adhesion protein 1 in hypertensive patients. J Am Soc Hypertens 9:855-864 12. Salmi M, Kalimo K, Jalkanen S (1993) Induction and function of vascular adhesion protein-1 at sites of inflammation. J Exp Med 178:2255-2260 13. Koc-Zorawska E, Malyszko J, Zbroch E, Malyszko J, Mysliwiec M (2012) Vascular adhesion protein-1 and renalase in regard to diabetes in hemodialysis patients. Arch Med Sci 8:1048-1052 14. Koc-Zorawska E, Malyszko J, Malyszko JS, Mysliwiec M (2012) VAP-1, a novel molecule linked to endothelial damage and kidney function in kidney allograft recipients. Kidney Blood Press Res 36:242-247 15. Lin MS, Li HY, Wei JN, Lin CH, Smith DJ, Vainio J et al (2008) Serum vascular adhesion protein-1 is higher in subjects with early stages of chronic kidney disease. Clin Biochem 41:1362-1367 16. Valente T, Gella A, Solé M, Durany N, Unzeta M (2012) Immunohistochemical study of semicarbazide-sensitive amine oxidase/vascular adhesion protein-1 in the hippocampal vasculature: pathological synergy of Alzheimer's disease and diabetes mellitus. J Neurosci Res 90:1989-1996 17. Murata M, Noda K, Fukuhara J, Kanda A, Kase S, Saito W et al (2012) Soluble vascular adhesion protein-1 accumulates in proliferative diabetic retinopathy. Invest Ophthalmol Vis Sci 53:4055-4062 18. Yanaba K, Yoshizaki A, Muroi E, Ogawa F, Shimizu K, Sato S (2013) Increased circulating soluble vascular adhesion protein-1 levels in systemic sclerosis: association with lower frequency and severity of interstitial lung disease. Int J Rheum Dis 16:442-447 19. Weston CJ, Shepherd EL, Claridge LC, Rantakari P, Curbishley SM, Tomlinson JW, et al (2015) Vascular adhesion protein-1 promotes liver inflammation and drives hepatic fibrosis. J Clin Invest. 125:501-20. 20. Wang YC, Li HY, Wei JN, Lin MS, Shih SR, Hua CH et al (2013) Serum vascular adhesion protein-1 level is higher in smokers than non-smokers. Ann Hum Biol 40:413-418 21. Li YI, Hung JS, Yu TY, Liou JM, Wei JN, Kao HL et al (2014) Serum vascular adhesion protein-1 predicts all-cause mortality and cancer-related mortality in subjects with colorectal cancer. Clin Chim Acta 428:51-56 22. Aalto K, Havulinna AS, Jalkanen S, Salomaa V, Salmi M (2014) Soluble vascular adhesion protein-1 predicts incident major adverse cardiovascular events and improves reclassification in a finnish prospective cohort study. Circ Cardiovasc Genet 7:529-535 23. Li HY, Jiang YD, Chang TJ, Wei JN, Lin MS, Lin CH et al (2011) Serum vascular adhesion protein-1 predicts 10-year cardiovascular and cancer mortality in individuals with type 2 diabetes. Diabetes 60:993-999 24. Yu TY, Li HY, Jiang YD, Chang TJ, Wei JN, Lin CM et al (2014) Serum vascular adhesion protein-1 level predicts risk of incident cancers in subjects with type II diabetes. Cancer Epidemiol Biomarkers Prev 23:1366-1373 25. Anger T, Pohle FK, Kandler L, Barthe T, Ensminger SM, Fischlein T et al (2007) VAP-1, Eotaxin3 and MIG as potential atherosclerotic triggers of severe calcified and stenotic human aortic valves: effects of statins. Exp Mol Pathol 83:435-442 26. Sun P, Solé M, Unzeta M (2014) Involvement of SSAO/VAP-1 in oxygen-glucose deprivation-mediated damage using the endothelial hSSAO/VAP-1-expressing cells as experimental model of cerebral ischemia. Cerebrovasc Dis 37:171-180 27. Xu HL, Garcia M, Testai F, Vetri F, Barabanova A, Pelligrino DA et al (2014) Pharmacologic blockade of vascular adhesion protein-1 lessens neurologic dysfunction in rats subjected to subarachnoid hemorrhage. Brain Res 1586:83-89 28. Katagiri D, Hamasaki Y, Doi K, Negishi K, Sugaya T, Nangaku M et al (2015) Interstitial renal fibrosis due to multiple cisplatin treatments is ameliorated by semicarbazide-sensitive amine oxidase inhibition. Kidney Int 10:1038 29. Lee WY, Salmi M, Kelly MM, Jalkanen S, Kubes P (2013) Therapeutic advantage of anti-VAP-1 over anti-α4 integrin antibody in concanavalin a-induced hepatitis. Hepatology. 58:1413-23. 30. Li R, Li H, Luo HJ, Lin ZX, Jiang ZW, Luo WH (2013) SSAO inhibitors suppress hepatocellular tumor growth in mice. Cell Immunol 283:61-69 31. Marttila-Ichihara F, Auvinen K, Elima K, Jalkanen S, Salmi M (2009) Vascular adhesion protein-1 enhances tumor growth by supporting recruitment of Gr-1+CD11b+ myeloid cells into tumors. Cancer Res 69:7875-83 32. Noda K, She H, Nakazawa T, Hisatomi T, Nakao S, Almulki L et al (2008) Vascular adhesion protein-1 blockade suppresses choroidal neovascularization. FASEB J 22:2928-35. 33. Foot JS, Yow TT, Schilter H, Buson A, Deodhar M, Findlay AD et al (2013) PXS-4681A, a potent and selective mechanism-based inhibitor of SSAO/VAP-1 with anti-inflammatory effects in vivo.J Pharmacol Exp Ther 347:365-374 34. Dunkel P, Gelain A, Barlocco D, Haider N, Gyires K, Sperlágh B et al (2008) Semicarbazide-sensitive amine oxidase/vascular adhesion protein 1: recent developments concerning substrates and inhibitors of a promising therapeutic target. Curr Med Chem 15:1827-1839 35. Chiu YF, Chuang LM, Hsiao CF, Hung YJ, Lin MW, Chen YT et al. An autosomal genome-wide scan for loci linked to pre-diabetic phenotypes in nondiabetic Chinese subjects from the Stanford Asia-Pacific Program of Hypertension and Insulin Resistance Family Study. Diabetes 2005;54:1200-1206. 36. Almasy L, Blangero J. Multipoint quantitative-trait linkage analysis in general pedigrees. Am J Hum Genet 1998;62:1198 –1211. 37. Abecasis GR, Cardon LR and Cookson WO. A general test of association for quantitative traits in nuclear families. Am J Hum Genet 2000;66:279-292. 38. Lander E, Kruglyak L. Genetic dissection of complex traits: guidelines for interpreting and reporting linkage results. Nat Genet 1995 Nov;11(3):241-7. 39. Rosenthal F, Feijs KL, Frugier E, Bonalli M, Forst AH, Imhof R et al (2013) Macrodomain-containing proteins are new mono-ADP-ribosylhydrolases. Nat Struct Mol Biol 20:502-507. 40. Feijs KL, Verheugd P, Lüscher B (2013) Expanding functions of intracellular resident mono-ADP-ribosylation in cell physiology. FEBS J 280:3519-3529. 41. Mohseni M, Cidado J, Croessmann S, Cravero K, Cimino-Mathews A, Wong HY et al (2014) MACROD2 overexpression mediates estrogen independent growth and tamoxifen resistance in breast cancers. Proc Natl Acad Sci U S A 111:17606-17611. 42. Briffa R, Um I, Faratian D, Zhou Y, Turnbull AK, Langdon SP et al (2015) Multi-Scale Genomic, Transcriptomic and Proteomic Analysis of Colorectal Cancer Cell Lines to Identify Novel Biomarkers. PLoS One 10:e0144708 43. Linnebacher M, Ostwald C, Koczan D, Salem T, Schneider B, Krohn M et al (2013) Single nucleotide polymorphism array analysis of microsatellite- stable,diploid/near- diploid coorectal carcinomas without the CpG island methylator phenotype. Oncol Lett 5:173-178. 44. Slavin TP, Feng T, Schnell A, Zhu X, Elston RC (2011) Two-marker association tests yield new disease associations for coronary artery disease and hypertension. Hum Genet 130:725-733. 45. Obeidat M, Wain LV, Shrine N, Kalsheker N, Soler-Artigas M, Repapi E et al (2011) A comprehensive evaluation of potential lung function associated genes in the SpiroMeta general population sample. PLoS One 6:e19382. 46. Julià A, Domènech E, Ricart E, Tortosa R, García-Sánchez V, Gisbert JP et al (2013) A genome-wide association study on a southern European population identifies a new Crohn's disease susceptibility locus at RBX1-EP300. Gut 62:1440-1445. 47. Anney R, Klei L, Pinto D, Regan R, Conroy J, Magalhaes TR et al (2010) A genome-wide scan for common alleles affecting risk for autism. Hum Mol Genet 19:4072-4082. 48. Lionel AC, Crosbie J, Barbosa N, Goodale T, Thiruvahindrapuram B, Rickaby J et al (2011) Rare copy number variation discovery and cross-disorder comparisons identify risk genes for ADHD. Sci Transl Med 3:95ra75. 49. Jahanshad N, Rajagopalan P, Hua X, Hibar DP, Nir TM, Toga AW et al (2013) Genome-wide scan of healthy human connectome discovers SPON1 gene variant influencing dementia severity. Proc Natl Acad Sci U S A 110:4768-4773. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/59512 | - |
| dc.description.abstract | 背景:血管附著蛋白-1(VAP-1) 是一種在成熟脂肪細胞中強烈表現的胺氧化酶，它是可溶性蛋白質並可分泌到細胞外，而血清中VAP-1之濃度與多種疾病有相關。本研究目的是找尋調控VAP-1血中濃度之基因。
材料方法:本研究針對史丹佛大學亞太地區高血壓和胰島素阻抗性計畫(SAPPHIRe)收集的398個家庭的1,100名受試者，研究血清中VAP-1數值的數量性狀之全基因組連鎖分析。另外使用單核苷酸多態性(SNPs)進行局部相關性細定位。 結果:估算之血清VAP-1數值的遺傳度很高(h2=69%)，血清VAP-1的數量性狀基因最顯著的位於第20號染色體38cM的位點上，LOD值為2.29(P=5.81×10-4)，女性更為顯著(LOD: 4.11, P=6.86×10-6)。在LOD值最顯著的區域正負1之區間使用SNP進行局部相關細定位，結果顯示MACROD2(MACRO domain containing 2)基因具有強烈的關聯性，尤其是在女性(P=5.38×10-6)。將MACROD2基因之表現抑制會顯著抑制人類初級脂肪細胞中VAP-1的表現量以及其分泌到培養基中之蛋白量。剔除MACROD2也顯著抑制脂肪細胞的分化。MACROD2表現與人類內臟脂肪組織中的VAP-1表現量呈正相關。此外，VAP-1表現量也與身體質量指數，胰島素阻抗性與空腹胰島素數值的體內平衡模型呈正相關，並與高密度脂蛋白膽固醇數值呈負相關。 結論:本研究顯示MACROD2是血清VAP-1濃度的潛在的遺傳因子決定因素，機轉可能是通過調節脂肪細胞的分化而影響VAP-1之表現量。 | zh_TW |
| dc.description.abstract | Background, Vascular adhesion protein-1 (VAP-1) is an amine oxidase that is strongly expressed in mature adipocytes and excreted as a soluble protein. Serum VAP-1 levels are associated with various diseases. The aim of this study is to identify the genetic factor that modulates expression of VAP-1.
Methods, We conducted a genome-wide linkage scan on 1,100 Han Chinese subjects from 398 families recruited in the Stanford Asian-Pacific Program for Hypertension and Insulin Resistance (SAPPHIRe) to map the quantitative trait loci (QTL) of circulating VAP-1 levels. We used additional single nucleotide polymorphisms (SNPs) association study for fine mapping. Results, The estimated heritability of circulating VAP-1 levels is high (h2=69%). The most significant QTL for circulating VAP-1 was located at 38 cM on chromosome 20, with a maximum empirical logarithm of odds (LOD) score of 2.29 (P=5.81×10-4), especially in females (LOD: 4.11, P=6.86×10-6). Regional SNP fine mapping within 1-unit support interval showed a strongest association signal in the MACROD2 (MACRO domain containing 2) gene, especially in females (P=5.38×10-6). The knockdown of MACROD2 significantly suppresses the expression of VAP-1 in primary human adipocytes and its secretion into the culture medium. Knockdown of MACROD2 also significantly suppresses the expression of key adipogenic genes. MACROD2 expression is positively associated with VAP-1 expression in human visceral adipose tissue. In addition, the expression level of VAP-1 is also positively associated with body mass index, homeostasis model assessment of insulin resistance (HOMA-IR) and fasting insulin levels and is negatively associated with high-density lipoprotein cholesterol (HDL-C) levels. Conclusion, Our study suggests MACROD2 is a potential genetic determinant of serumVAP-1 levels, probably through regulation of adipogenesis. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-16T09:26:10Z (GMT). No. of bitstreams: 1 ntu-106-P04448004-1.pdf: 1080416 bytes, checksum: 2aa2be701ff3c5567645a334f92ab342 (MD5) Previous issue date: 2017 | en |
| dc.description.tableofcontents | 謝誌 i
中文摘要 ii ABSTRACT iii CONTENTS v LIST OF FIGURES vi LIST OF TABLES vii Chapter 1 Introduction 1 Chapter 2 Methods and Materials 3 2.1 The SAPPHIRe study cohort 3 2.2 Genotyping and single nucleotide polymorphism(SNP) imputation 3 2.3 Subjects for measurement of gene expression in adipose tissue 4 2.4 Human adipocyte culture 4 2.5 Knockdown of MACROD2 in induced human adipocytes 5 2.6 Reverse transcription and quantitative real-time PCR 5 2.7 Statistical analysis 6 2.8 Linkage analysis 6 2.9 Association analysis 7 Chapter 3 Result 8 Chapter 4 Discussion 10 Chapter 5 Conclusions 12 Reference 23 | |
| dc.language.iso | en | |
| dc.subject | 脂肪細胞分化 | zh_TW |
| dc.subject | 相關分析 | zh_TW |
| dc.subject | 連鎖分析 | zh_TW |
| dc.subject | 血管附著蛋白-1 | zh_TW |
| dc.subject | MACROD2 | zh_TW |
| dc.subject | 脂肪細胞分化 | zh_TW |
| dc.subject | 相關分析 | zh_TW |
| dc.subject | 連鎖分析 | zh_TW |
| dc.subject | 血管附著蛋白-1 | zh_TW |
| dc.subject | MACROD2 | zh_TW |
| dc.subject | association analysis | en |
| dc.subject | VAP-1 | en |
| dc.subject | linkage analysis | en |
| dc.subject | adipogenesis | en |
| dc.subject | MACROD2 | en |
| dc.subject | VAP-1 | en |
| dc.subject | linkage analysis | en |
| dc.subject | association analysis | en |
| dc.subject | adipogenesis | en |
| dc.subject | MACROD2 | en |
| dc.title | 血清VAP-1全基因組之連鎖分析:
MACROD2 調節脂肪分化的角色 | zh_TW |
| dc.title | A genome-wide linkage analysis for circulating
vascular adhesion protein -1 levels: MACROD2 as a regulator of adipogenesis | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 105-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.coadvisor | 莊立民(Lee-Ming Chuang) | |
| dc.contributor.oralexamcommittee | 張以承(Yi-cheng Chang) | |
| dc.subject.keyword | 血管附著蛋白-1,連鎖分析,相關分析,脂肪細胞分化,MACROD2, | zh_TW |
| dc.subject.keyword | VAP-1,linkage analysis,association analysis,adipogenesis,MACROD2, | en |
| dc.relation.page | 28 | |
| dc.identifier.doi | 10.6342/NTU201700887 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2017-06-06 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 分子醫學研究所 | zh_TW |
| 顯示於系所單位： | 分子醫學研究所 | |
文件中的檔案：
| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| ntu-106-1.pdf 未授權公開取用 | 1.06 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。