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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 李永凌 | |
| dc.contributor.author | Nai-Wei Kuo | en |
| dc.contributor.author | 郭乃文 | zh_TW |
| dc.date.accessioned | 2021-06-08T00:11:56Z | - |
| dc.date.copyright | 2013-09-24 | |
| dc.date.issued | 2013 | |
| dc.date.submitted | 2013-08-06 | |
| dc.identifier.citation | 1. Halbert AR, Weston WL, Morelli JG. Atopic dermatitis: is it an allergic disease? J Am Acad Dermatol 1995; 33:1008-18.
2. Leung DY, Diaz LA, DeLeo V, Soter NA. Allergic and immunologic skin disorders. JAMA 1997; 278:1914-23. 3. Lapidus CS, Schwarz DF, Honig PJ. Atopic dermatitis in children: who cares? Who pays? J Am Acad Dermatol 1993; 28:699-703. 4. Hwang CY, Chen YJ, Lin MW, Chen TJ, Chu SY, Chen CC, et al. Prevalence of atopic dermatitis, allergic rhinitis and asthma in Taiwan: a national study 2000 to 2007. Acta Derm Venereol 2010; 90:589-94. 5. Yi O, Kwon HJ, Kim H, Ha M, Hong SJ, Hong YC, et al. Effect of environmental tobacco smoke on atopic dermatitis among children in Korea. Environ Res 2012; 113:40-5. 6. Adham TM, Tawfik SA, Abdo NM. House dust mites in pediatric atopic dermatitis. Saudi Med J 2011; 32:177-82. 7. Namkung JH, Lee JE, Kim E, Kim HJ, Seo EY, Jang HY, et al. Association of polymorphisms in genes encoding IL-4, IL-13 and their receptors with atopic dermatitis in a Korean population. Exp Dermatol 2011; 20:915-9. 8. Masuoka M, Shiraishi H, Ohta S, Suzuki S, Arima K, Aoki S, et al. Periostin promotes chronic allergic inflammation in response to Th2 cytokines. J Clin Invest 2012; 122:2590-600. 9. Zurawski SM, Chomarat P, Djossou O, Bidaud C, McKenzie AN, Miossec P, et al. The primary binding subunit of the human interleukin-4 receptor is also a component of the interleukin-13 receptor. J Biol Chem 1995; 270:13869-78. 10. Kuperman D, Schofield B, Wills-Karp M, Grusby MJ. Signal transducer and activator of transcription factor 6 (Stat6)-deficient mice are protected from antigen-induced airway hyperresponsiveness and mucus production. J Exp Med 1998; 187:939-48. 11. Tomkinson A, Kanehiro A, Rabinovitch N, Joetham A, Cieslewicz G, Gelfand EW. The failure of STAT6-deficient mice to develop airway eosinophilia and airway hyperresponsiveness is overcome by interleukin-5. Am J Respir Crit Care Med 1999; 160:1283-91. 12. Chang YT, Lee WR, Yu CW, Liu HN, Lin MW, Huang CH, et al. No association of cytokine gene polymorphisms in Chinese patients with atopic dermatitis. Clin Exp Dermatol 2006; 31:419-23. 13. Tamura K, Arakawa H, Suzuki M, Kobayashi Y, Mochizuki H, Kato M, et al. Novel dinucleotide repeat polymorphism in the first exon of the STAT-6 gene is associated with allergic diseases. Clin Exp Allergy 2001; 31:1509-14. 14. Kavalar MS, Balantic M, Silar M, Kosnik M, Korosec P, Rijavec M. Association of ORMDL3, STAT6 and TBXA2R gene polymorphisms with asthma. Int J Immunogenet 2012; 39:20-5. 15. Li Y, Wu B, Xiong H, Zhu C, Zhang L. Polymorphisms of STAT-6, STAT-4 and IFN-gamma genes and the risk of asthma in Chinese population. Respir Med 2007; 101:1977-81. 16. Gao PS, Mao XQ, Roberts MH, Arinobu Y, Akaiwa M, Enomoto T, et al. Variants of STAT6 (signal transducer and activator of transcription 6) in atopic asthma. J Med Genet 2000; 37:380-2. 17. Tung KY, Tsai CH, Lee YL. Microsomal epoxide hydroxylase genotypes/diplotypes, traffic air pollution, and childhood asthma. Chest 2011; 139:839-48. 18. Tsai CH, Tung KY, Chen CH, Lee YL. Tumour necrosis factor G-308A polymorphism modifies the effect of home dampness on childhood asthma. Occup Environ Med 2011; 68:771-6. 19. Wang IJ, Tsai CH, Chen CH, Tung KY, Lee YL. Glutathione S-transferase, incense burning and asthma in children. Eur Respir J 2011; 37:1371-7. 20. 41st World Medical Assembly. Declaration of Helsinki: recommendations guiding physicians in biomedical research involving human subjects. Bull Pan Am Health Organ. 1990; 24:606 - 9. 21. Patel BK, Keck CL, O'Leary RS, Popescu NC, LaRochelle WJ. Localization of the human stat6 gene to chromosome 12q13.3-q14.1, a region implicated in multiple solid tumors. Genomics 1998; 52:192-200. 22. Tong IS, Lu Y. Identification of confounders in the assessment of the relationship between lead exposure and child development. Ann Epidemiol 2001; 11:38-45. 23. Stram DO, Leigh Pearce C, Bretsky P, Freedman M, Hirschhorn JN, Altshuler D, et al. Modeling and E-M estimation of haplotype-specific relative risks from genotype data for a case-control study of unrelated individuals. Hum Hered 2003; 55:179-90. 24. Schedel M, Frei R, Bieli C, Cameron L, Adamski J, Lauener R, et al. An IgE-associated polymorphism in STAT6 alters NF-kappaB binding, STAT6 promoter activity, and mRNA expression. J Allergy Clin Immunol 2009; 124:583-9, 9 e1-6. 25. Dotterud LK, Odland JO, Falk ES. Atopic dermatitis and respiratory symptoms in Russian and northern Norwegian school children: a comparison study in two arctic areas and the impact of environmental factors. J Eur Acad Dermatol Venereol 2004; 18:131-6. 26. Al-Sahab B, Atoui M, Musharrafieh U, Zaitoun F, Ramadan F, Tamim H. Epidemiology of eczema among Lebanese adolescents. Int J Public Health 2008; 53:260-7. 27. Kilpelainen M, Terho EO, Helenius H, Koskenvuo M. Home dampness, current allergic diseases, and respiratory infections among young adults. Thorax 2001; 56:462-7. 28. Zirngibl A, Franke K, Gehring U, von Berg A, Berdel D, Bauer CP, et al. Exposure to pets and atopic dermatitis during the first two years of life. A cohort study. Pediatr Allergy Immunol 2002; 13:394-401. 29. Weidinger S, Klopp N, Wagenpfeil S, Rummler L, Schedel M, Kabesch M, et al. Association of a STAT 6 haplotype with elevated serum IgE levels in a population based cohort of white adults. J Med Genet 2004; 41:658-63. 30. Kabesch M, Schedel M, Carr D, Woitsch B, Fritzsch C, Weiland SK, et al. IL-4/IL-13 pathway genetics strongly influence serum IgE levels and childhood asthma. J Allergy Clin Immunol 2006; 117:269-74. 31. Pykalainen M, Kinos R, Valkonen S, Rydman P, Kilpelainen M, Laitinen LA, et al. Association analysis of common variants of STAT6, GATA3, and STAT4 to asthma and high serum IgE phenotypes. J Allergy Clin Immunol 2005; 115:80-7. 32. Howell MD, Gao P, Kim BE, Lesley LJ, Streib JE, Taylor PA, et al. The signal transducer and activator of transcription 6 gene (STAT6) increases the propensity of patients with atopic dermatitis toward disseminated viral skin infections. J Allergy Clin Immunol 2011; 128:1006-14. 33. Wu H, Romieu I, Shi M, Hancock DB, Li H, Sienra-Monge JJ, et al. Evaluation of candidate genes in a genome-wide association study of childhood asthma in Mexicans. J Allergy Clin Immunol 2010; 125:321-7 e13. 34. Levin AM, Mathias RA, Huang L, Roth LA, Daley D, Myers RA, et al. A meta-analysis of genome-wide association studies for serum total IgE in diverse study populations. J Allergy Clin Immunol 2013; 131:1176-84. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/17420 | - |
| dc.description.abstract | 背景:
異位性皮膚炎是在孩童及嬰兒間相當常見的慢性、過敏性疾病，而訊息傳遞及轉錄因子6 (STAT6) 蛋白在致敏的機制中扮演重要腳色，其基因多型性會影響其蛋白的功能，可能進而影響疾病，不過STAT6 基因多型性和異位性皮膚炎的關係還是需要進一步進行確認。 方法: 研究對象取自台灣14個鄉鎮的國中小，共收了5,915位學孩童。STAT6基因單一核苷酸多型性(SNP)資料是取自International HapMap Project，以北京漢人及日本人做為分析對象，利用Haploview及連鎖不平衡選取四個tag SNPs，分別是rs703817、 rs324015、rs3024974及SNP rs324011，來探討STAT6基因多型性對孩童異位性皮膚炎的影響。 針對前面流行病學研究中有意義的位點，我們對其前後做細部定序，並對細部定序後所發現的新位點進行第二次相關性研究及in vitro functional assays。 結果: 在分析的四個位點中，rs324011和孩童異位性皮膚炎有顯著相關 (Recessive model: OR=1.6, FDR=0.02; Additive model: OR=1.2, FDR=0.06)。之後，針對 rs324011前後進行細部定序發現五個SNP，分析後發現rs167769 達到邊緣顯著，帶有T對偶基因的孩童有較高的危險，Odds ratio為1.2 (95%信賴區間為1.0-1.5，p值是0.06)，另外在in vitro functional assays中我們也發現，T對偶基因會提高STAT6 基因啟動子的活性。 結論: STAT6 基因上的 rs324011及rs167769 和孩童異位性皮膚炎的易感受有關，帶有T對偶基因的孩童有較高的危險，此外，T對偶基因會提高STAT6 基因啟動子的活性。 | zh_TW |
| dc.description.abstract | Background:
Atopic dermatitis (AD) is a chronic inflammatory skin disease mainly affecting children and infants. The Signal Transducer and Activator of Transcription 6 (STAT6) genetic variants regulate STAT6 protein which takes roles in allergic pathway. The relationship between STAT6 gene and AD needs further investigation. Methods: This study recruited 5,915 children from public schools in 14 Taiwanese communities. We used Hapmap dataset of Han Chinese to choose four tag SNPs (rs703817, rs324015, rs3024974 and rs324011) by Haploview and investigated the relationship between STAT6 gene and AD. We performed deep sequencing around the variant highly associated with AD and then conducted a second association study in our population. Furthermore, in vitro functional assays were used to verify the significant findings. Results: In our children’s cohort, the variant rs324011 revealed a positive effect on the occurrence of AD (Recessive model: OR=1.6, FDR=0.02; Additive model: OR=1.2, FDR=0.06). After deep sequencing, we identified five new targeted variants around rs324011 (rs167769, rs324012, rs3024948, rs117195019, and rs118014438). Among these variants, rs167769 showed a borderline statistical significance (unadjusted OR=1.21, p=0.07; adjusted OR=1.22, p=0.06). Children with variant rs167769 T allele had a higher risk to suffer from AD. Using in vitro luciferase assay, we also found the polymorphic T allele at rs167769 was associated with higher promoter activity of STAT6 gene. Conclusions: The STAT6 variants rs324011 and rs167769 are associated with AD susceptibility, and the polymorphic T allele at rs167769 would increase promoter activity in vitro. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-08T00:11:56Z (GMT). No. of bitstreams: 1 ntu-102-R00849017-1.pdf: 880453 bytes, checksum: 40f380a1e3a0bc052a9c6d4114d0c8dc (MD5) Previous issue date: 2013 | en |
| dc.description.tableofcontents | Directory
1 Introduction 1 1.1 Study Background 1 1.2 Aim of this Study 2 2 Literature Review 3 2.1 Atopic dermatitis 3 2.2 Signal Transducer and Activator of Transcription 6 (STAT6) 4 2.3 The relationship between STAT6 and AD 5 2.4 The Gap and limitation of Previous Study 5 3 Methods and Materials 7 3.1 Study Flow 7 3.2 Study population 7 3.3 Variants selection and genotyping 8 3.4 Deep sequencing 10 3.5 The 2nd Association Study 10 3.6 STAT6 vector constructs 11 3.7 Jurkat cell line 11 3.8 STAT6 vector transfection experiments 12 3.9 Statistical Analysis 12 4 Results 15 4.1 Characteristics of the TCHS population 15 4.2 Main effects of each variants for childhood AD 15 4.3 Identification of genetic variants near STAT6 variant rs324011 16 4.4 In silico prediction 17 4.5 The 2nd association study 18 4.6 Functional assay 19 5 Discussion 20 5.1 The relationship between STAT6 gene and childhood AD 20 5.2 Covariates 21 5.3 STAT6 variant rs324011 22 5.4 STAT6 variant rs167769 23 5.5 Strength and Limitation of the Study 24 5.6 Future perspective 24 6 Conclusion 26 7 References 27 Directory of Tables Table 1. Review of studies concerning about STAT6 gene variants and allergic diseases. 33 Table 2. Characteristics of our TCHS study population in part2. 37 Table 3. Genotype frequencies of STAT6 in part2. 39 Table 4. Pairwise measures of linkage disequilibrium for STAT6 gene. 41 Table 5. Association of STAT6 genetic variants with AD in part2. 42 Table 6. Haplotype frequencies of STAT6 gene. 45 Table 7. Association of STAT6 haplotypes with AD in part2. 46 Table 8. Location of variants around rs324011 by deep sequencing in part3. 47 Table 9. In silico prediction of 6 new targeted Variants around rs324011by TFSEARCH. 48 Table 10. Association of new targeted variants of STAT6 gene with AD in part4. 49 Directory of Figures Figure 1. Study flowchart of this study. 52 Figure 2. Variants and pairwise linkage disequilibrium map of the STAT6 gene from HapMap database in part1. 53 Figure 3. Variants and pairwise linkage disequilibrium map of the variants around rs324011. 54 Figure 4. The construct of the STAT6 rs167769 vector. 55 Figure 5 In vitro STAT6 promoter activity depending on rs167769. 56 | |
| dc.language.iso | en | |
| dc.title | 探討STAT6基因變異點與異位性皮膚炎的易感性 | zh_TW |
| dc.title | Variants of Signal Transducer and Activator of Transcription 6 Gene and Susceptibility of Atopic Dermatitis | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 101-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 郭柏秀,徐立中,王怡人 | |
| dc.subject.keyword | 異位性皮膚炎,基因多型性,STAT6,Signal Transducer and Activator of Transcription 6,Jurkat cells, | zh_TW |
| dc.subject.keyword | Atopic dermatitis,Genetic polymorphism,STAT6,Signal Transducer and Activator of Transcription 6,Jurkat cells, | en |
| dc.relation.page | 55 | |
| dc.rights.note | 未授權 | |
| dc.date.accepted | 2013-08-06 | |
| 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 |
| 顯示於系所單位： | 流行病學與預防醫學研究所 | |
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