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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 張以承 | zh_TW |
| dc.contributor.advisor | Yi-Cheng Chang | en |
| dc.contributor.author | 楊為舜 | zh_TW |
| dc.contributor.author | Wei-shun Yang | en |
| dc.date.accessioned | 2024-08-19T17:00:02Z | - |
| dc.date.available | 2024-08-20 | - |
| dc.date.copyright | 2024-08-19 | - |
| dc.date.issued | 2024 | - |
| dc.date.submitted | 2024-07-12 | - |
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Vassalotti JA, Centor R, Turner BJ, Greer RC, Choi M, Sequist TD, et al. Practical Approach to Detection and Management of Chronic Kidney Disease for the Primary Care Clinician. Am J Med. 2016;129(2):153-62 e7. | - |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/94822 | - |
| dc.description.abstract | 介紹：慢性腎臟疾病對全球健康造成巨大負擔，其定義包含腎小球過濾率降低及白蛋白尿。族群特定的相關基因在全基因組相關研究中經常被觀察到。本研究針對台灣非糖尿病人群進行白蛋白尿尿的全基因組相關研究，並且利用大型前瞻性研究探討蛋白尿在感染造成住院率之關係。
方法：本研究從台灣生物資料庫招募了30-70歲、無癌症病史的非糖尿病人群，其中有6,768名受試者進行了尿液檢驗。使用PLINK進行品質控制並使用SHAPEIT和IMPUTE2進行填補，並排除了等位基因頻率低於0.1%的單核苷酸多態性(SNP)，最終共保留了3,638,350個單核苷酸多態性(SNP)，使用線性回歸分析了單核苷酸多態性(SNP)與白蛋白尿/尿肌酐比值之間的關係。此外本研究利用2005年至2008年間參與新北市健康篩檢計畫的慢性腎病1–3期患者，以比例危險回歸模型計算了年輕（<50歲）和老年（≥50歲）慢性腎病患者感染相關住院和死亡的危險比（HR）和95%的信賴區間（CI）以及蛋白尿在兩族群中的影響。 結果：全基因組相關分析(GWAS)顯示在FCRL3（p = 2.56 × 10-6）、TMEM161（p = 4.43 × 10-6）、EFCAB1（p = 2.03 × 10-6）、ELMOD1（p = 2.97 × 10-6）、RYR3（p = 1.34 × 10-6）和PIEZO2（p = 2.19 × 10-7）的附近或內部識別了六個可能位點。FCRL3基因中編碼分泌型IgA受體的遺傳變異與IgA腎病有關，後者可表現為蛋白尿。PIEZO2基因編碼了腎絲球髓質細胞和產腎素細胞中的機械力感應器。還在五個基因中識別到五個p值介於5 × 10-6和5 × 10-5之間的單核苷酸多態性(SNP)，這些基因可能在白蛋白尿的發展中具有生物學作用。 我們並發現蛋白尿與感染引發住院的風險明顯相關, 且獨立於估計腎小球濾過率（eGFR）而這種關係在年長者中更明顯。 結論：在台灣非糖尿病人群中識別了五個新的位點和一個已知的可能位點與白蛋白尿相關，而且蛋白尿與感染造成住院之風險明顯相關，尤其於年長族群。 | zh_TW |
| dc.description.abstract | Introduction: Chronic kidney disease, which is defined by a reduced estimated glomerular filtration rate and albuminuria, imposes a large health burden worldwide, including infection associated complications. Ethnicity-specific associations are frequently observed in genome-wide association studies (GWAS). This study conducts a GWAS of albuminuria and a prospective study of albuminuria associated infection-complication in Taiwanese population.
Methods: Nondiabetic individuals aged 30-70 years without a history of cancer were enrolled from the Taiwan Biobank. A total of 6,768 subjects were subjected to a spot urine examination. After quality control using PLINK and imputation using SHAPEIT and IMPUTE2, a total of 3,638,350 single-nucleotide polymorphisms (SNPs) remained for testing. SNPs with a minor allele frequency of less than 0.1% were excluded. Linear regression was used to determine the relationship between SNPs and log urine albumin-to-creatinine ratio. A proportional hazards regression model was employed to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) for infection-related hospitalization and mortality in 119,871 Taiwanese adults. Results: GWAS identified six suggestive loci are identified in or near the FCRL3 (p = 2.56 × 10-6), TMEM161 (p = 4.43 × 10-6), EFCAB1 (p = 2.03 × 10-6), ELMOD1 (p = 2.97 × 10-6), RYR3 (p = 1.34 × 10-6), and PIEZO2 (p = 2.19 × 10-7). Genetic variants in the FCRL3 gene that encode a secretory IgA receptor are found to be associated with IgA nephropathy, which can manifest as proteinuria. The PIEZO2 gene encodes a sensor for mechanical forces in mesangial cells and renin-producing cells. Five SNPs with a p-value between 5 × 10-6 and 5 × 10-5 are also identified in five genes that may have a biological role in the development of albuminuria. Proteinuria increases the risk of infection-related hospitalization independently of estimated glomerular filtration rate (eGFR), and this relationship is stronger in elderly individuals. Conclusion: Five new loci and one known suggestive locus for albuminuria are identified in the nondiabetic Taiwanese population. The risk of infection-related hospitalization is higher in the elderly with proteinuria. | en |
| dc.description.provenance | Submitted by admin ntu (admin@lib.ntu.edu.tw) on 2024-08-19T17:00:02Z No. of bitstreams: 0 | en |
| dc.description.provenance | Made available in DSpace on 2024-08-19T17:00:02Z (GMT). No. of bitstreams: 0 | en |
| dc.description.tableofcontents | 口試委員會審定書 i
致謝 ii 中文摘要 iii 英文摘要 iv 第一章 背景與文獻回顧 1 第一節 白蛋白尿與慢性腎臟病的意義 1 第二節 全基因組相關研究 6 第三節 腎臟疾病相關之全基因組相關研究 10 第四節 臨床上白蛋白尿對感染症之影響 14 第二章 研究目的 15 第三章 研究方法 16 A. 白蛋白尿全基因組相關研究 16 第一節 材料及方法 16 第二節 驗證 17 第三節 統計分析 17 B. 白蛋白尿與感染症住院的關係 18 第一節 資料來源與研究對象 18 第二節 測量參數 19 第三節 結果 19 第四節 統計分析 20 第五節 倫理 20 第四章 研究結果 21 A. 白蛋白尿全基因組相關研究 21 B. 蛋白尿與感染症住院的關係 31 第五章 綜合討論 35 第六章 結論 40 第七章 未來應用與研究方向 41 圖次 圖一. KDIGO (Kidney Disease: Improving Global Outcomes) 慢性腎臟病治療指引慢性腎病之分期 2 圖二. 健康足細胞中間隙隔膜信號級聯和肌動蛋白動態之間的示意性互動 3 圖三. 蛋白尿和白蛋白尿病理機轉 5 圖四. 全基因組相關研究示意圖 9 圖五. 歐洲族群的白蛋白尿全基因組相關研究 10 圖六 . 日本的白蛋白尿全基因組相關研究 11 圖七. p <5.0 × 10−6的曼哈頓圖(Manhattan plot) 23 圖八. Q-Q plot 24 圖九. 六個單核苷酸多態性(SNP)的區域圖 25 表次 表一 . 與蛋白尿性腎病相關的裂隙隔膜和肌動蛋白細胞骨架的基因 4 表二. 腎臟病相關之全基因組相關研究文獻回顧 12 表三. 研究族群基本資料 21 表四 在6,768 名非糖尿病台灣人中可能與白蛋白尿相關的單核苷酸多態性(SNP) (p < 5x 10-6) 22 表五. p值介於5× 10-6和10-4的單核苷酸多態性(SNP)及其鄰近基因 27 表六. 與CKDgen進行驗證 28 表七. 與UK Biobank 驗證 30 表八. 新北健檢基本資料(以年齡分層) (N = 119,871) 32 表九. 慢性腎病分期以及蛋白尿程度在年輕(小於五十歲)和年長(大於等於50歲)族群與感染住院風險的關聯 34 參考文獻 42 附件 著作列表 51 | - |
| dc.language.iso | zh_TW | - |
| dc.subject | 全基因組相關分析(GWAS) | zh_TW |
| dc.subject | 蛋白尿 | zh_TW |
| dc.subject | 住院 | zh_TW |
| dc.subject | 感染 | zh_TW |
| dc.subject | 白蛋白尿 | zh_TW |
| dc.subject | genome-wide association study | en |
| dc.subject | hospitalization | en |
| dc.subject | infection | en |
| dc.subject | proteinuria | en |
| dc.subject | albuminuria | en |
| dc.title | 白蛋白尿在台灣族群的全基因組相關分析(GWAS)以及蛋白尿與感染住院的關係 | zh_TW |
| dc.title | A Genome-Wide Association Studies for Albuminuria and the Association of Proteinuria with Infection-associated Hospitalization in Taiwanese Population | en |
| dc.type | Thesis | - |
| dc.date.schoolyear | 112-2 | - |
| dc.description.degree | 博士 | - |
| dc.contributor.oralexamcommittee | 莊立民;許書睿;賴台軒;徐治平 | zh_TW |
| dc.contributor.oralexamcommittee | LEE-MING CHUANG;SHU-JUI HSU;Tau-shuan Lai;Chir-ping Hsu | en |
| dc.subject.keyword | 白蛋白尿,蛋白尿,全基因組相關分析(GWAS),感染,住院, | zh_TW |
| dc.subject.keyword | albuminuria,proteinuria,genome-wide association study,infection,hospitalization, | en |
| dc.relation.page | 52 | - |
| dc.identifier.doi | 10.6342/NTU202401448 | - |
| dc.rights.note | 同意授權(全球公開) | - |
| dc.date.accepted | 2024-07-15 | - |
| dc.contributor.author-college | 醫學院 | - |
| dc.contributor.author-dept | 基因體暨蛋白體醫學研究所 | - |
| 顯示於系所單位： | 基因體暨蛋白體醫學研究所 | |
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