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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/123456789/7063
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dc.contributor.advisor程蘊菁(Yen-Ching Chen)
dc.contributor.authorChine-Lin Maoen
dc.contributor.author毛健麟zh_TW
dc.date.accessioned2021-05-17T10:18:08Z-
dc.date.available2015-03-02
dc.date.available2021-05-17T10:18:08Z-
dc.date.copyright2012-03-02
dc.date.issued2011
dc.date.submitted2011-11-09
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dc.identifier.urihttp://tdr.lib.ntu.edu.tw/jspui/handle/123456789/7063-
dc.description.abstract背景:Secreted phosphoprotein-1 (SPP1) 骨橋蛋白基因,藉由和破骨細胞膜表面的vitronectin受體結合,參與破骨細胞接合骨質的破骨作用中。最近的統合分析發現,SPP1基因多型性與骨密度及骨折的風險有關。
方法:這是一篇橫斷式研究。 1319位健康台灣女性,年齡在40至55歲,於2009年10月至2010年8月間,從美兆健康體檢中心被招募。高與低骨密度比較,高骨密度定義為三等分的第一組,而第二組加上第三組則為低骨密度。本研究探討三種常見的(對偶基因頻率> 5%) haplotype-tagging單核苷酸多型性(htSNP)來分析SPP1基因多型性與低骨密度風險的關聯。我們還評估了更年期,年齡,身體質量指數和相關的生物標誌物如何影響SPP1多型性與低骨密度風險之間的相關
結果:研究結果顯示帶有rs4754變異的對偶基因會降低低骨密度風險[2 vs. 0 copies: adjust odds ratio(AOR)= 0.54,95%CI= 0.36 - 0.81],與非攜帶者相比,攜帶兩個變異的婦女有較高的骨密度。在單倍體分析方面,在校正偽陽性率後,攜帶HAP1 TGC兩個變異的婦女在高鹼性磷酸酶 [AOR= 0.30,95%CI= 0.15 - 0.64]和或低尿酸 [AOR= 0.33,95%CI= 0.16 - 0.68] 時有保護的效果。 SPP1基因和低骨密度風險,無論是在單核苷酸多型性或單倍體水平沒有顯著作用。在本研究中,停經與否並不會顯著的修飾SPP1基因與低骨密度的關係。
結論:在中年亞裔女性身上,SPP1基因多型性與保護骨密度低下有顯著的相關。
zh_TW
dc.description.abstractBackground. Secreted phosphoprotein-1 (SPP1) is involved in the anchoring of osteoclasts to the mineral of bone matrix by binding with vitronectin receptor. A recent meta-analysis found SPP1 genetic polymorphisms were associated with bone mineral density (BMD) and fracture risk.
Methods. This is a cross-sectional study. A total of 1,319 healthy Taiwanese women aged 40 to 55 years old were recruited from MJ health screening center from October 2009 to August 2010. High versus low bone mineral density (BMD) was defined as the 1st tertile versus 2nd plus 3rd tertiles of BMD. Three common (allele frequency>5%) haplotype-tagging single nucleotide polymorphisms (htSNPs) were selected to examine the association between sequence variants of SPP1 and BMD.
Results. Women carrying two copies of variant rs4754 had a significantly decreased risk of low BMD [adjusted OR (AOR) = 0.54, 95% CI = 0.36 - 0.81] as compared with non-carriers. Women carrying two copies of minor haplotype TGC had a decreased risk of low BMD among those with high alkaline phosphatase [AOR = 0.30, 95% CI = 0.15 - 0.64] or with low uric acid [AOR = 0.33, 95% CI = 0.16 - 0.68]. These associations remained significantly associated with low BMD after controlling for FDR. Menopausal status did not significant modify the association between SPP1 polymorphisms and low BMD.
Conclusion . Genetic polymorphisms of SPP1 were significantly associated with decreased risk of low BMD in middle-aged Asian women.
en
dc.description.provenanceMade available in DSpace on 2021-05-17T10:18:08Z (GMT). No. of bitstreams: 1
ntu-100-R98846001-1.pdf: 2498240 bytes, checksum: 21a2a0f21ab395abcd932baa768e6502 (MD5)
Previous issue date: 2011
en
dc.description.tableofcontentsContents
口試委員會審定書 i
致謝 ii
摘要 iii
ABSTRACT v
Contents 1
List of figures 3
List of tables 4
Chapter 1. INTRODUCTION 6
1.1 Osteoporosis (OP) and bone mineral density (BMD) 6
1.2 Secreted phosphoprotein-1 (SPP1) gene 7
1.3 Associations between SPP1 polymorphisms and OP or BMD 7
1.4 Aims 8
Chapter 2. MATERIALS AND METHODS 9
2.1 Study population 9
2.2 Bone mineral density measurement 9
2.3 SNP selection and genotyping assays 10
2.4 Statistical analyses 10
Chapter 3. RESULTS 13
3.1 Characteristics of the study population 13
3.2 SPP1 polymorphisms and BMD 13
3.3 SPP1 haplotypes and BMD 14
3.4 Effect modification by potential confounders 15
Chapter 4. DISCUSSIONS 17
4.1 Main findings 17
4.2 Postulated Mechanism of SPP1 and low BMD 18
4.3 Strengths and Limitations 21
Chapter 5. CONCLUSIONS 23
Reference 24
 
List of figures
Figure 1. The flowchart of participant recruitment 29
Figure 2. Distribution of BMD 30
Figure 3. Linkage disequilibrium (LD) plot of SPP1 gene 31
Figure 4. Mean bone mineral density (BMD) ± 1 standard error (SE) in the different rs11730582 genotype groups. 32
Figure 5. Mean bone mineral density (BMD) ± 1 standard error (SE) in the different rs6839524 genotype groups. 33
Figure 6. Mean bone mineral density (BMD) ± 1 standard error (SE) in the different rs4754 genotype groups. 34
Figure 7. Postulated mechanisms of SPP1 and BMD 35
Figure 8. Forest plot of low BMD risk for different covariates 36
 
List of tables
Table 1. Definition of low and high BMD groups 37
Table 2. Characteristics of the study population 38
Table 3. Characteristics of SPP1 haplotype-tagging SNPs 39
Table 4. SPP1 SNPs and the risk of low BMD 40
Table 5. SPP1 haplotypes and the risk of low BMD 41
Table 6. SPP1 SNPs and the risk of low BMD by menopausal status 42
Table 7. SPP1 SNPs and the risk of low BMD by BMI 43
Table 8. SPP1 SNPs and the risk of low BMD by serum ALP level (low and high) 44
Table 9. SPP1 SNPs and the risk of low BMD by serum creatinine level (low and high) 45
Table 10. SPP1 SNPs and the risk of low BMD by serum UA level (low and high) 46
Table 11. SPP1 SNPs and the risk of low BMD by serum LDL level (low and high) 47
Table 12. SPP1 haplotypes and the risk of low BMD by menopausal status 48
Table 13. SPP1 haplotypes and the risk of low BMD by BMI 49
Table 14. SPP1 haplotypes and the risk of low BMD by ALP level (low and high) 50
Table 15. SPP1 haplotypes and the risk of low BMD by creatinine level (low and high) 51
Table 16. SPP1 haplotypes and the risk of low BMD by UA level (low and high) 52
Table 17. SPP1 haplotypes and the risk of low BMD by serum LDL level (low and high) 53
Table 18. Interaction between rs4754 and serum biomarkers on low BMD risk 54
Table 19. Interaction between HAP1 and serum biomarkers on low BMD risk 55
Table 20. Previous studies on SPP1 polymorphisms and BMD 56
dc.language.isoen
dc.subject單倍型zh_TW
dc.subject單倍型zh_TW
dc.subject酸多型性zh_TW
dc.subject骨橋蛋白zh_TW
dc.subject骨質密度zh_TW
dc.subject骨質疏鬆症zh_TW
dc.subject單核&#33527zh_TW
dc.subjecthaplotypesen
dc.subjectSPP1en
dc.subjectosteopontinen
dc.subjectosteoporosisen
dc.subjectbone mineral densityen
dc.subjectsingle nucleotide polymorphismen
dc.title台灣女性SPP1基因多型性與骨密度低下之關聯研究zh_TW
dc.titleSecreted Phosphoprotein-1 (SPP1) Polymorphisms Are Associated with a Decreased Risk of Low Bone Mineral Density in Taiwanese Womenen
dc.typeThesis
dc.date.schoolyear100-1
dc.description.degree碩士
dc.contributor.oralexamcommittee丘政民,簡國龍,李文宗,蔡克嵩
dc.subject.keyword骨質疏鬆症,骨質密度,骨橋蛋白,單倍型,單核&#33527,酸多型性,單倍型,zh_TW
dc.subject.keywordSPP1,osteopontin,osteoporosis,bone mineral density,single nucleotide polymorphism,haplotypes,en
dc.relation.page56
dc.rights.note同意授權(全球公開)
dc.date.accepted2011-11-10
dc.contributor.author-college公共衛生學院zh_TW
dc.contributor.author-dept流行病學與預防醫學研究所zh_TW
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