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  1. NTU Theses and Dissertations Repository
  2. 公共衛生學院
  3. 流行病學與預防醫學研究所
請用此 Handle URI 來引用此文件: http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/90215
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dc.contributor.advisor程藴菁zh_TW
dc.contributor.advisorYen-Ching Chenen
dc.contributor.author蘇盈豪zh_TW
dc.contributor.authorYing-Hao Suen
dc.date.accessioned2023-09-22T17:53:26Z-
dc.date.available2023-11-09-
dc.date.copyright2023-09-22-
dc.date.issued2023-
dc.date.submitted2023-08-09-
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27. Nsengiyumva V, Krishna SM, Moran CS, Moxon JV, Morton SK, Clarke MW, et al. Vitamin D deficiency promotes large rupture-prone abdominal aortic aneurysms and cholecalciferol supplementation limits progression of aneurysms in a mouse model. Clin Sci (Lond). 2020;134(18):2521-34.
28. Enkhjargal B, McBride DW, Manaenko A, Reis C, Sakai Y, Tang J, et al. Intranasal administration of vitamin D attenuates blood-brain barrier disruption through endogenous upregulation of osteopontin and activation of CD44/P-gp glycosylation signaling after subarachnoid hemorrhage in rats. J Cereb Blood Flow Metab. 2017;37(7):2555-66.
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32. Estimating dose-response relationships for vitamin D with coronary heart disease, stroke, and all-cause mortality: observational and Mendelian randomisation analyses. Lancet Diabetes Endocrinol. 2021;9(12):837-46.
33. Zhou A, Selvanayagam JB, Hyppönen E. Non-linear Mendelian randomization analyses support a role for vitamin D deficiency in cardiovascular disease risk. Eur Heart J. 2022;43(18):1731-9.
34. Michaëlsson K, Wolk A, Byberg L, Mitchell A, Mallmin H, Melhus H. The seasonal importance of serum 25-hydroxyvitamin D for bone mineral density in older women. J Intern Med. 2017;281(2):167-78.
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48. Lips P, van Schoor NM. The effect of vitamin D on bone and osteoporosis. Best Pract Res Clin Endocrinol Metab. 2011;25(4):585-91.
49. LeBoff MS, Chou SH, Murata EM, Donlon CM, Cook NR, Mora S, et al. Effects of Supplemental Vitamin D on Bone Health Outcomes in Women and Men in the VITamin D and OmegA-3 TriaL (VITAL). J Bone Miner Res. 2020;35(5):883-93.
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dc.identifier.urihttp://tdr.lib.ntu.edu.tw/jspui/handle/123456789/90215-
dc.description.abstract目標:
本研究目的在檢驗以下兩點:1)25-羥基膽鈣化醇濃度與骨密度之間的線性和非線性關聯性;以及2)SPP1(secreted phosphoprotein 1)基因多態性與維生素D缺乏對骨密度的聯合影響。
方法:
此橫斷面研究共招募了657名中年女性,其中包括524名停經前及133位停經後。利用雙能量X光吸光式測定儀測量了腰椎的面積性骨密度(g/cm2)。我們從SPP1基因中選擇了三個標記SNP作分析(rs11730582來自啟動子,rs6839524來自外顯子,rs4754來自內含子)。我們用不同方法評估了25-羥基膽鈣化醇對骨密度的影響,作為連續變項、序列變項(三分等級)或二元變項(維生素D缺乏,臨界值25-羥基膽鈣化醇 <20 ng/mL)指標。根據女性的更年期狀態,低骨密度的定義有所不同。在停經前女性中,以Z分數(Z-score)落在最低四分位數內定義為低骨密度。相反,在停經後女性中,低骨密度定義包括帶有骨質稀少(osteopenia)或骨質疏鬆症(osteoporosis)。
結果:
中年女性併維生素D缺乏會增加低骨密度風險(調整過的勝算比在停經前女性為1.65,95%信賴區間為1.06-2.61;停經後女性其調整過的勝算比3.04,95%信賴區間為1.08-9.36),在調整了年齡、BMI (body mass index)、體脂肪、測量維生素D的季節、體力活動、鈣質補充和久坐工作後。多項式回歸分析顯示25-羥基膽鈣化醇的二次項為顯著,在停經前和停經後婦女中,25-羥基膽鈣化醇濃度與低骨密度風險之間呈倒J型關係。停經後且維生素D充足的女性,若攜帶rs11730582 變異體或者包含等位基因的 CCT 單倍體,則會有減少的低骨密度風險;然而,停經後女性併維生素D缺乏且攜帶 rs6839524 變異體,或者攜帶 rs4754 野生型基因,則有上升的低骨密度風險。
結論:
我們的結果表示,充足的維生素D濃度在中年女性的骨質健康扮演角色。且維他命D濃度與低骨密度風險間有非線性關係。停經後女性較易受到SPP1基因多態性和維生素D缺乏的聯合影響。
zh_TW
dc.description.abstractObjectives: The study aimed to investigate the followings: 1) the association of 25-hydroxycholecalciferol levels with bone mineral density (BMD) using linear and nonlinear analyses, and 2) the joint effect of secreted phosphoprotein 1 (SPP1) genetic polymorphisms and vitamin D deficiency on BMD.
Materials and methods: A total of 657 women, including 524 premenopausal and 133 postmenopausal individuals, were enrolled. Areal BMD (g/cm2) of the lumbar spine was measured by dual-energy X-ray absorptiometry. Three tagging single nucleotides polymorphisms (SNPs) from promotor (rs11730582), exon (rs6839524), and intron (rs4754) were selected from the SPP1 gene. The effect of 25-hydroxycholecalciferol on BMD was assessed as a continuous, ordinal (tertile), or dichotomous (vitamin D deficiency with a cut-off value of 25-hydroxycholecalciferol < 20 ng/mL) indicator. Low BMD was characterized differently depending on the menopausal status of the women. In premenopausal women, it was determined by a Z-score that fell within the lowest quartile. Conversely, in postmenopausal women, the definition included the presence of osteopenia or osteoporosis.
Results: A significant association of vitamin D deficiency with the risk of low BMD was observed in premenopausal (adjusted odds ratio [aOR]: 1.65, 95% confidence interval [CI]: 1.06-2.61) and postmenopausal women (aOR: 3.04, 95% CI 1.08-9.36), after adjustments for age, body mass index, body fat percentages, seasons of blood collection, physical activity, calcium supplementations, and sedentary work. Nonlinear, polynomial regression analyses indicated that the quadratic term of 25-hydroxycholecalciferol levels was significant and a reverse J-shaped relationship between 25-hydroxycholecalciferol levels and the risk of low BMD in midlife women was found. Postmenopausal, vitamin D-repleted women who carry rs11730582 variant or the haplotype CCT have a reduced risk of low BMD, while vitamin D-deficient, postmenopausal women carrying rs6839524 variant or rs4754 wild type have an elevated risk of low BMD.
Conclusion: Adequate vitamin D levels play a role in bone health in midlife women. A nonlinear association of 25-hydroxycholecalciferol levels with the risk of low BMD was observed. Postmenopausal women may be susceptible to the joint effect of vitamin D deficiency and SPP1 genetic polymorphisms.
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dc.description.tableofcontents口試委員會審定書 i
誌謝 ii
中文摘要 iii
英文摘要 v
目錄 vii
圖目錄 ix
表目錄 x
1. Introduction 1
1.1 Osteoporosis 1
1.2 Vitamin D 1
1.3 Effects of SPP1 genetic polymorphisms on BMD 2
1.4 Research gaps and study aims 2
2. Materials and Methods 4
2.1 Study design and population 4
2.2 Assessment of BMD 4
2.3 Assessment of vitamin D level and covariates 5
2.4 Genotyping 5
2.5 Statistical analyses 6
3. Results 8
3.1 Descriptive statistics 8
3.2 Vitamin D effect by logistic regression analysis 8
3.3 Vitamin D effect by nonlinear regression analysis 9
3.4 The joint effect of vitamin D deficiency and SPP1 genetic polymorphism 9
3.5 Post-hoc power analyses and Comparison of model fits 10
4. Results 11
4.1 Main findings 11
4.2 Postulated Mechanism 11
4.3 Comparison with previous studies 12
4.4 Strengths of this study 14
4.5 Limitations of this study 14
4.6 Clinical implications 15
5. Conclusion 16
References 17
-
dc.language.isoen-
dc.subject骨橋蛋白zh_TW
dc.subject維他命Dzh_TW
dc.subject骨質稀少zh_TW
dc.subject單核苷多樣性zh_TW
dc.subject骨質密度zh_TW
dc.subject骨質疏鬆zh_TW
dc.subject分泌磷蛋白1zh_TW
dc.subjectosteopeniaen
dc.subjectvitamin Den
dc.subjectbone mineral densityen
dc.subjectosteopontinen
dc.subjectsecreted phosphoprotein 1en
dc.subjectsingle nucleotide polymorphismsen
dc.subjectosteoporosisen
dc.title維生素D 缺乏症和SPP1(骨橋蛋白)遺傳多態性與 中年女性骨密度的相互關係。橫斷面研究zh_TW
dc.titleThe intercorrelation of vitamin D deficiency and SPP1 (Osteopontin) genetic polymorphisms with bone mineral density in middle-aged women. A cross-sectional studyen
dc.typeThesis-
dc.date.schoolyear111-2-
dc.description.degree碩士-
dc.contributor.oralexamcommittee蔡克嵩;陳人豪;馮嬿臻zh_TW
dc.contributor.oralexamcommitteeKeh-Sung Tsai;Jen-Hau Chen;Yen-Chen Anne Fengen
dc.subject.keyword維他命D,骨質密度,骨橋蛋白,分泌磷蛋白1,單核苷多樣性,骨質疏鬆,骨質稀少,zh_TW
dc.subject.keywordvitamin D,bone mineral density,osteopontin,secreted phosphoprotein 1,single nucleotide polymorphisms,osteoporosis,osteopenia,en
dc.relation.page35-
dc.identifier.doi10.6342/NTU202303591-
dc.rights.note同意授權(限校園內公開)-
dc.date.accepted2023-08-09-
dc.contributor.author-college公共衛生學院-
dc.contributor.author-dept流行病學與預防醫學研究所-
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