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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 張以承 | |
| dc.contributor.author | Chen-Hao Huang | en |
| dc.contributor.author | 黃振豪 | zh_TW |
| dc.date.accessioned | 2021-06-16T16:42:29Z | - |
| dc.date.available | 2025-08-26 | |
| dc.date.copyright | 2020-08-26 | |
| dc.date.issued | 2020 | |
| dc.date.submitted | 2020-04-16 | |
| dc.identifier.citation | 1. Degirolamo, C., Sabba, C., and Moschetta, A. (2016) Therapeutic potential of the endocrine fibroblast growth factors FGF19, FGF21 and FGF23, Nature reviews. Drug discovery 15, 51-69.
2. Kanbay, M., Vervloet, M., Cozzolino, M., et al. (2016) Novel Faces of Fibroblast Growth Factor 23 (FGF23): Iron Deficiency, Inflammation, Insulin Resistance, Left Ventricular Hypertrophy, Proteinuria and Acute Kidney Injury, Calcified tissue international. 3. Kestenbaum, B., Sachs, M. C., Hoofnagle, A. N., et al. (2014) Fibroblast Growth Factor-23 and Cardiovascular Disease in the General Population The Multi-Ethnic Study of Atherosclerosis, Circ-Heart Fail 7, 409-U457. 4. Angelin, B., Larsson, T. E., and Rudling, M. (2012) Circulating Fibroblast Growth Factors as Metabolic Regulators-A Critical Appraisal, Cell Metab 16, 693-705. 5. Mirza, M. A. I., Alsio, J., Hammarstedt, A., et al. (2011) Circulating Fibroblast Growth Factor-23 Is Associated With Fat Mass and Dyslipidemia in Two Independent Cohorts of Elderly Individuals, Arterioscl Throm Vas 31, 219-227. 6. Garland, J. S., Holden, R. M., Ross, R., et al. (2014) Insulin resistance is associated with Fibroblast Growth Factor-23 in stage 3-5 chronic kidney disease patients, J Diabetes Complicat 28, 61-65. 7. Jones, E.Y., Fugger, L., Strominger, J.L., Siebold, C. (2006) MHC class II proteins and disease: a structural perspective. Nat Rev Immunol, 6, 271-282. 8. Delaneau, O., Zagury, J.F. and Marchini, J. (2013) Improved whole-chromosome phasing for disease and population genetic studies. Nat Methods, 10, 5-6. 9. Howie, B., Fuchsberger, C., Stephens, M., Marchini, J. and Abecasis, G.R. (2012) Fast and accurate genotype imputation in genome-wide association studies through pre-phasing. Nat Genet, 44, 955-959. 10. di Giuseppe, R., Buijsse, B., Hirche, F., et al. (2014) Plasma Fibroblast Growth Factor 23, Parathyroid Hormone, 25-Hydroxyvitamin D3, and Risk of Heart Failure: A Prospective, Case-Cohort Study, J Clin Endocr Metab 99, 947-955. 11. di Giuseppe, R., Kuhn, T., Hirche, F., et al. (2015) Plasma fibroblast growth factor 23 and risk of cardiovascular disease: results from the EPIC-Germany case-cohort study, Eur J Epidemiol 30, 131-141. 12. Panwar, B., Jenny, N. S., Howard, V. J., et al. (2015) Fibroblast Growth Factor 23 and Risk of Incident Stroke in Community-Living Adults, Stroke 46, 322-328. 13. Turner, S. (2014) qqman: an R package for visualizing GWAS results using Q-Q and manhattan plots. 14. Team, R.D.C. (2008) R: A language and environment for statistical computing, R Foundation for Statistical Computing, Vienna, Austria. 15. Pruim, R.J., Welch, R.P., Sanna, S., Teslovich, T.M., Chines, P.S., Gliedt, T.P., Boehnke, M., Abecasis, G.R. and Willer, C.J. (2010) LocusZoom: regional visualization of genome-wide association scan results. Bioinformatics, 26, 2336-2337. 16. Pekkinen, M., Laine, C. M., Makitie, R., et al. (2015) FGF23 gene variation and its association with phosphate homeostasis and bone mineral density in Finnish children and adolescents, Bone 71, 124-130. 17. Schjoldager KT, Vester-Christensen MB, Goth CK, et al. (2011) systematic study of site-specific GalNAc-type O-glycosylation modulating proprotein convertase processing, J Biol Chem 286, 40122-40132. 18. Nabil G. Seidah (2011) What lies ahead for the proprotein convertases? Ann N Y Acad Sci 1220,149-161. 19. Martina Feger, Philipp Hase, Bingbing Zhang, et al. (2017) The production of fibroblast growth factor 23 is controlled by TGF-β2, Sci Rep 7, 4982 20. Cassianne Robinson-Cohen , Traci M. Bartz, Dongbing Lai, et al. (2018) Genetic Variants Associated with Circulating Fibroblast Growth Factor 23, J Am Soc Nephrol 29, 2583–2592. 21. Chen, C.H., Yang, J.H., Chiang, C.W.K., Hsiung, C.N., Wu, P.E., Chang, L.C., Chu, H.W., Chang, J., Song, I.W., Yang, S.L. et al. (2016) Population structure of Han Chinese in the modern Taiwanese population based on 10,000 participants in the Taiwan Biobank project. Hum Mol Genet, 25, 5321-5331. 22. Purcell, S., Neale, B., Todd-Brown, K., Thomas, L., Ferreira, M.A., Bender, D., Maller, J., Sklar, P., de Bakker, P.I., Daly, M.J. et al. (2007) PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet, 81, 559-575. 23. Andrew Beenken & Moosa Mohammadi (2009) The FGF family: biology, pathophysiology and therapy. Nat. Rev. Drug Discov. 8, 235–253 | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/63449 | - |
| dc.description.abstract | 研究背景
纖維母細胞生長因子家族成員目前發現有22種，這些蛋白質參與多種關鍵的生理功能，FGF23屬於FGF家族成員之一為內分泌賀爾蒙。近期發現纖維母細胞生長因子23（fibroblast growth factor 23, FGF23）有別於過去的認知，不只調節磷酸恆定和維生素D代謝，更參與多項代謝異常。遺傳研究有助於瞭解複雜性性狀與疾病的機轉，我們進行了台灣第一個全基因組關聯研究（GWAS），找尋影響血清FGF23濃度之基因位點。 研究方法 我們招募了來自Taiwan Biobank的5,000名參與者，進行了全基因組關聯研究（GWAS），利用酵素連結免疫吸附分析法測定血清FGF23的濃度。並使用PLINK v1.07中的additive genetic model進行GWAS分析。在排除患有糖尿病和品質控管未通過的參與者後，共分析了4201名受試者其單核苷酸多型性（SNP）與進行對數轉換的FGF23濃度的關聯，調整了年齡和性別。 結果 我們分析了4201位非糖尿病受試者，以P<1.0 x 10-6為閾值，找到3個SNP與血清FGF23濃度相關，位於PCSK9基因附近的SNP rs17111495、TGFβ2基因內的SNP rs2798631、HLA-DQA1基因附近的SNP rs17843626與血清中的FGF23水平顯示出統計學上的顯著關聯（分別為P = 4.88 x 10-10、P = 6.46 x 10-7和P = 3.74 x 10-8）。 結論 我們發現位於PCSK9基因附近、TGFβ2基因內、HLA-DQA1基因附近 SNP與華人血清中的FGF23濃度具有相關性。需要進一步的研究以支持我們的發現。 | zh_TW |
| dc.description.abstract | There are 22 members of the fibroblast growth factor family currently. These proteins are involved in many physiological functions. As endocrine hormone, FGF23 belongs to one of the members of the FGF family. Recent studies have found that fibroblast growth factor 23 (FGF23) is different from prior understanding. It not only regulates phosphate homeostasis and vitamin D metabolism but also participates in metabolic disturbances. Genetic studies are helpful to understand the complex traits and the mechanism of disease. We conducted the first whole genome association study (GWAS) in Taiwan to find genetic loci that affect serum FGF23 concentration.
We recruited 5,000 participants from Taiwan Biobank. We performed a genome-wide association study (GWAS) and measured the concentration of serum FGF23 by enzyme-linked immunosorbent assay. GWAS analysis was performed by the additive genetic model in PLINK v1.07. After excluding participants with diabetes and failed quality control, a total of 4201 subjects were analyzed for associations between their single nucleotide polymorphisms (SNPs) and logarithmic FGF23 concentrations, adjusting for age and gender. We analyzed 4201 non-diabetic subjects. Using P <1.0 x 10-6 as the threshold, we found 3 SNPs that are related to serum FGF23 concentration. These associated SNPs are located at or adjacent to PCSK9, TGFβ2 and HLA-DQA1and show a statistically significant correlation with serum FGF23 levels (P = 4.88 x 10-10, P = 6.46 x 10-7, and P = 3.74 x 10-8, respectively). | en |
| dc.description.provenance | Made available in DSpace on 2021-06-16T16:42:29Z (GMT). No. of bitstreams: 1 ntu-109-P07448012-1.pdf: 2237986 bytes, checksum: 5fe29c36449b56eed056391c45d8cc43 (MD5) Previous issue date: 2020 | en |
| dc.description.tableofcontents | 中文摘要………………………………………………………………………….......ii
英文摘要………………………………………………………………………………iii 第一章研究背景與動機………………………………………………… …………...vi 1. 前言… … … … … … … … ………………………………………………vi 2. 纖維母細胞生長因子23(FGF23)… ………………………………………vi 3. 纖維母細胞生長因子23（FGF23）與胰島素抗性… … .. ……………....vii 4. 纖維母細胞生長因子23（FGF23）的遺傳關聯研究（genetic association study）… … … … … … …………………………………………………..vii 第二章 研究方法……………………………………………………………………viii 1. 研究對象……………………………………………………………………viii 2. FGF23測量…………………………………………………………………viii 3. 基因型分型、填補及品管………………………………………………….viii 4. 統計分析… … … … ……………………………………………………..ix 第三章 結果………………………………………………………………..………x 1. 基本生理資料… .. ………………………………………………………..x 2. 關聯性分析結果……………………………………………………….….x 第四章 討論……………………………………………………………..……..….12 Table 1………………………………………………………………………………14 Table 2………………………………………………………………………………15 Table 3………………………………………………………………………………16 Table 4………………………………………………………………………………17 Table 5……………………………………………………………………………...18 Table 6……………………………………………………………………………...19 Figure 1……………………………………………………………………………..14 Figure 2……………………………………………………………………………..20 Figure 3……………………………………………………………………………..21 Figure 4……………………………………………………………………………..21 附錄一………………………………………………………………………………23 附錄二………………………………………………………………………………25 附錄三………………………………………………………………………………28 第五章 參考文獻………………………………………………………………… 30 | |
| dc.language.iso | zh-TW | |
| dc.subject | 內分泌 | zh_TW |
| dc.subject | 單一核甘酸多型性 | zh_TW |
| dc.subject | 磷酸鹽恆定 | zh_TW |
| dc.subject | 全基因組關聯性分析 | zh_TW |
| dc.subject | 纖維母細胞生長因子23 | zh_TW |
| dc.subject | endocrine | en |
| dc.subject | fibroblast growth factor 23 | en |
| dc.subject | Genome-wide association study | en |
| dc.subject | phosphate homeostasis | en |
| dc.subject | Single Nucleotide Polymorphism. | en |
| dc.title | 人類血清FGF23濃度的全基因組相關研究 | zh_TW |
| dc.title | Genome-Wide Association Study of Serum FGF23 Levels | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 108-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 許書睿,劉碧華 | |
| dc.subject.keyword | 纖維母細胞生長因子23,全基因組關聯性分析,磷酸鹽恆定,內分泌,單一核甘酸多型性, | zh_TW |
| dc.subject.keyword | fibroblast growth factor 23,Genome-wide association study,phosphate homeostasis,endocrine,Single Nucleotide Polymorphism., | en |
| dc.relation.page | 32 | |
| dc.identifier.doi | 10.6342/NTU202000743 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2020-04-21 | |
| 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 | |
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