請用此 Handle URI 來引用此文件：
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/29591完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 胡忠怡 | |
| dc.contributor.author | Sheng-Kai Zhang | en |
| dc.contributor.author | 張勝凱 | zh_TW |
| dc.date.accessioned | 2021-06-13T01:11:26Z | - |
| dc.date.available | 2012-08-08 | |
| dc.date.copyright | 2007-08-08 | |
| dc.date.issued | 2007 | |
| dc.date.submitted | 2007-07-20 | |
| dc.identifier.citation | 1. Chou, C. T., L. Pei, D. M. Chang, C. F. Lee, H. R. Schumacher, and M. H. Liang. 1994. Prevalence of rheumatic diseases in Taiwan: a population study of urban, suburban, rural differences. J. Rheumatol. 21:302.
2. Clegg, D. O., and J. R. Ward. 1987. Diagnostic criteria in rheumatoid arthritis. Scand. J. Rheumatol. Suppl 65:3. 3. Yen, J. H., J. R. Chen, W. J. Tsai, J. J. Tsai, and H. W. Liu. 1995. HLA-DRB1 genotyping in patients with rheumatoid arthritis in Taiwan. J. Rheumatol. 22:1450. 4. Sulitzeanu, D., and M. Anafi. 1989. EBV, molecular mimicry and rheumatoid arthritis: a hypothesis. Immunol. Lett. 20:89, 93, 95. 5. Einsele, H., M. Steidle, C. A. Muller, P. Fritz, J. Zacher, H. Schmidt, and J. G. Saal. 1992. Demonstration of cytomegalovirus (CMV) DNA and anti-CMV response in the synovial membrane and serum of patients with rheumatoid arthritis. J. Rheumatol. 19:677. 6. Bas, S. 2005. [Usefulness of anti-citrullinated protein antibodies in the diagnosis and prognosis of rheumatoid arthritis]. Rev. Med. Suisse 1:674, 677, 680. 7. Verheijden, G. F., A. W. Rijnders, E. Bos, C. J. Coenen-de Roo, C. J. van Staveren, A. M. Miltenburg, J. H. Meijerink, D. Elewaut, K. F. de, E. Veys, and A. M. Boots. 1997. Human cartilage glycoprotein-39 as a candidate autoantigen in rheumatoid arthritis. Arthritis Rheum. 40:1115. 8. McColl, G. J., D. S. Cram, and L. C. Harrison. 1995. Antibodies to synovial antigens in recent-onset rheumatoid arthritis. Arthritis Rheum. 38:1418. 9. van Schooten, W. C., D. Devereux, C. H. Ho, J. Quan, B. A. Aguilar, and C. J. Rust. 1994. Joint-derived T cells in rheumatoid arthritis react with self-immunoglobulin heavy chains or immunoglobulin-binding proteins that copurify with immunoglobulin. Eur. J. Immunol. 24:93. 10. Lee, Y. H., J. D. Ji, and G. G. Song. 2007. Tumor necrosis factor-alpha promoter -308 A/G polymorphism and rheumatoid arthritis susceptibility: a metaanalysis. J. Rheumatol. 34:43. 11. Balog, A., J. Gal, Z. Gyulai, S. Zsilak, and Y. Mandi. 2004. Tumour necrosis factor-alpha and heat-shock protein 70-2 gene polymorphisms in a family with rheumatoid arthritis. Acta Microbiol. Immunol. Hung. 51:263. 12. Lard, L. R., F. A. van Gaalen, J. J. Schonkeren, E. J. Pieterman, G. Stoeken, K. Vos, R. G. Nelissen, R. G. Westendorp, R. C. Hoeben, F. C. Breedveld, R. E. Toes, and T. W. Huizinga. 2003. Association of the -2849 interleukin-10 promoter polymorphism with autoantibody production and joint destruction in rheumatoid arthritis. Arthritis Rheum. 48:1841. 13. Padyukov, L., A. M. Hytonen, M. Smolnikova, M. Hahn-Zoric, N. Nilsson, L. A. Hanson, A. Tarkowski, and L. Klareskog. 2004. Polymorphism in promoter region of IL10 gene is associated with rheumatoid arthritis in women. J. Rheumatol. 31:422. 14. Hajeer, A. H., M. Lazarus, D. Turner, R. A. Mageed, J. Vencovsky, P. Sinnott, I. V. Hutchinson, and W. E. Ollier. 1998. IL-10 gene promoter polymorphisms in rheumatoid arthritis. Scand. J. Rheumatol. 27:142. 15. Sivalingam, S. P., J. Thumboo, S. Vasoo, S. T. Thio, C. Tse, and K. Y. Fong. 2007. In vivo pro- and anti-inflammatory cytokines in normal and patients with rheumatoid arthritis. Ann. Acad. Med. Singapore 36:96. 16. Doring, G. 1994. The role of neutrophil elastase in chronic inflammation. Am. J. Respir. Crit Care Med. 150:S114-S117. 17. Rannou, F., M. Francois, M. T. Corvol, and F. Berenbaum. 2006. Cartilage breakdown in rheumatoid arthritis. Joint Bone Spine 73:29. 18. Ma, Y., and R. M. Pope. 2005. The role of macrophages in rheumatoid arthritis. Curr. Pharm. Des 11:569. 19. Simon, G. H., H. E. drup-Link, and E. J. Rummeny. 2007. [Macrophage specific MRI imaging for antigen induced arthritides : A potential new strategy for the diagnosis of rheumatoid arthritis.]. Radiologe 47:43. 20. Samanta, A., S. Roy, J. Feehally, and D. P. Symmons. 1992. The prevalence of diagnosed systemic lupus erythematosus in whites and Indian Asian immigrants in Leicester city, UK. Br. J. Rheumatol. 31:679. 21. Hochberg, M. C. 1997. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 40:1725. 22. Maraina, C. H., M. D. Kamaliah, and M. Ishak. 2004. The autoantibody profile and its association with clinical manifestations in Malay SLE patients. Asian Pac. J. Allergy Immunol. 22:33. 23. Toubi, E., and Y. Shoenfeld. 2007. Clinical and biological aspects of anti-P-ribosomal protein autoantibodies. Autoimmun. Rev. 6:119. 24. Graham, R. R., W. Ortmann, P. Rodine, K. Espe, C. Langefeld, E. Lange, A. Williams, S. Beck, C. Kyogoku, K. Moser, P. Gaffney, P. K. Gregersen, L. A. Criswell, J. B. Harley, and T. W. Behrens. 2007. Specific combinations of HLA-DR2 and DR3 class II haplotypes contribute graded risk for disease susceptibility and autoantibodies in human SLE. Eur. J. Hum. Genet. 25. Dunckley, H., P. A. Gatenby, and S. W. Serjeantson. 1986. DNA typing of HLA-DR antigens in systemic lupus erythematosus. Immunogenetics 24:158. 26. Sirikong, M., N. Tsuchiya, D. Chandanayingyong, S. Bejrachandra, P. Suthipinittharm, K. Luangtrakool, D. Srinak, R. Thongpradit, U. Siriboonrit, and K. Tokunaga. 2002. Association of HLA-DRB1*1502-DQB1*0501 haplotype with susceptibility to systemic lupus erythematosus in Thais. Tissue Antigens 59:113. 27. Hirankarn, N., J. Wongpiyabovorn, O. Hanvivatvong, J. Netsawang, S. Akkasilpa, J. Wongchinsri, P. Hanvivadhanakul, W. Korkit, and Y. Avihingsanon. 2006. The synergistic effect of FC gamma receptor IIa and interleukin-10 genes on the risk to develop systemic lupus erythematosus in Thai population. Tissue Antigens 68:399. 28. Chu, Z. T., N. Tsuchiya, C. Kyogoku, J. Ohashi, Y. P. Qian, S. B. Xu, C. Z. Mao, J. Y. Chu, and K. Tokunaga. 2004. Association of Fcgamma receptor IIb polymorphism with susceptibility to systemic lupus erythematosus in Chinese: a common susceptibility gene in the Asian populations. Tissue Antigens 63:21. 29. Graham, R. R., S. V. Kozyrev, E. C. Baechler, M. V. Reddy, R. M. Plenge, J. W. Bauer, W. A. Ortmann, T. Koeuth, M. F. Gonzalez Escribano, B. Pons-Estel, M. Petri, M. Daly, P. K. Gregersen, J. Martin, D. Altshuler, T. W. Behrens, and M. E. arcon-Riquelme. 2006. A common haplotype of interferon regulatory factor 5 (IRF5) regulates splicing and expression and is associated with increased risk of systemic lupus erythematosus. Nat. Genet. 38:550. 30. Lin, P. W., C. M. Huang, C. C. Huang, C. H. Tsai, J. J. Tsai, C. P. Chang, and F. J. Tsai. 2007. The association of -627 interleukin-10 promoter polymorphism in Chinese patients with systemic lupus erythematosus. Clin. Rheumatol. 26:298. 31. Lu, L. Y., H. H. Cheng, P. K. Sung, M. H. Tai, J. J. Yeh, and A. Chen. 2005. Tumor necrosis factor-beta +252A polymorphism is associated with systemic lupus erythematosus in Taiwan. J. Formos. Med. Assoc. 104:563. 32. Chen, J. Y., C. M. Wang, C. C. Ma, Y. H. Chow, and S. F. Luo. 2005. The -844C/T polymorphism in the Fas ligand promoter associates with Taiwanese SLE. Genes Immun. 6:123. 33. Gaipl, U. S., L. E. Munoz, G. Grossmayer, K. Lauber, S. Franz, K. Sarter, R. E. Voll, T. Winkler, A. Kuhn, J. Kalden, P. Kern, and M. Herrmann. 2007. Clearance deficiency and systemic lupus erythematosus (SLE). J. Autoimmun. 28:114. 34. Grossmayer, G. E., L. E. Munoz, U. S. Gaipl, S. Franz, A. Sheriff, R. E. Voll, J. R. Kalden, and M. Herrmann. 2005. Removal of dying cells and systemic lupus erythematosus. Mod. Rheumatol. 15:383. 35. Gaipl, U. S., A. Kuhn, A. Sheriff, L. E. Munoz, S. Franz, R. E. Voll, J. R. Kalden, and M. Herrmann. 2006. Clearance of apoptotic cells in human SLE. Curr. Dir. Autoimmun. 9:173. 36. Munoz, L. E., U. S. Gaipl, S. Franz, A. Sheriff, R. E. Voll, J. R. Kalden, and M. Herrmann. 2005. SLE--a disease of clearance deficiency? Rheumatology. (Oxford) 44:1101. 37. Gaipl, U. S., R. E. Voll, A. Sheriff, S. Franz, J. R. Kalden, and M. Herrmann. 2005. Impaired clearance of dying cells in systemic lupus erythematosus. Autoimmun. Rev. 4:189. 38. Kirschfink, M., F. Petry, K. Khirwadkar, R. Wigand, J. P. Kaltwasser, and M. Loos. 1993. Complete functional C1q deficiency associated with systemic lupus erythematosus (SLE). Clin. Exp. Immunol. 94:267. 39. Tsukumo, S., and K. Yasutomo. 2004. DNaseI in pathogenesis of systemic lupus erythematosus. Clin. Immunol. 113:14. 40. Hanayama, R., K. Miyasaka, M. Nakaya, and S. Nagata. 2006. MFG-E8-dependent clearance of apoptotic cells, and autoimmunity caused by its failure. Curr. Dir. Autoimmun. 9:162. 41. Hanayama, R., M. Tanaka, K. Miyasaka, K. Aozasa, M. Koike, Y. Uchiyama, and S. Nagata. 2004. Autoimmune disease and impaired uptake of apoptotic cells in MFG-E8-deficient mice. Science 304:1147. 42. Liu, F. T., K. Albrandt, E. Mendel, A. Kulczycki, Jr., and N. K. Orida. 1985. Identification of an IgE-binding protein by molecular cloning. Proc. Natl. Acad. Sci. U. S. A 82:4100. 43. Barondes, S. H., V. Castronovo, D. N. Cooper, R. D. Cummings, K. Drickamer, T. Feizi, M. A. Gitt, J. Hirabayashi, C. Hughes, K. Kasai, and . 1994. Galectins: a family of animal beta-galactoside-binding lectins. Cell 76:597. 44. Gritzmacher, C. A., V. S. Mehl, and F. T. Liu. 1992. Genomic cloning of the gene for an IgE-binding lectin reveals unusual utilization of 5' untranslated regions. Biochemistry 31:9533. 45. Raimond, J., D. B. Zimonjic, C. Mignon, M. Mattei, N. C. Popescu, M. Monsigny, and A. Legrand. 1997. Mapping of the galectin-3 gene (LGALS3) to human chromosome 14 at region 14q21-22. Mamm. Genome 8:706. 46. Kadrofske, M. M., K. P. Openo, and J. L. Wang. 1998. The human LGALS3 (galectin-3) gene: determination of the gene structure and functional characterization of the promoter. Arch. Biochem. Biophys. 349:7. 47. Flotte, T. J., T. A. Springer, and G. J. Thorbecke. 1983. Dendritic cell and macrophage staining by monoclonal antibodies in tissue sections and epidermal sheets. Am. J. Pathol. 111:112. 48. Moutsatsos, I. K., M. Wade, M. Schindler, and J. L. Wang. 1987. Endogenous lectins from cultured cells: nuclear localization of carbohydrate-binding protein 35 in proliferating 3T3 fibroblasts. Proc. Natl. Acad. Sci. U. S. A 84:6452. 49. Liu, F. T., D. K. Hsu, R. I. Zuberi, I. Kuwabara, E. Y. Chi, and W. R. Henderson, Jr. 1995. Expression and function of galectin-3, a beta-galactoside-binding lectin, in human monocytes and macrophages. Am. J. Pathol. 147:1016. 50. Truong, M. J., V. Gruart, F. T. Liu, L. Prin, A. Capron, and M. Capron. 1993. IgE-binding molecules (Mac-2/epsilon BP) expressed by human eosinophils. Implication in IgE-dependent eosinophil cytotoxicity. Eur. J. Immunol. 23:3230. 51. Craig, S. S., P. Krishnaswamy, A. M. Irani, C. L. Kepley, F. T. Liu, and L. B. Schwartz. 1995. Immunoelectron microscopic localization of galectin-3, an IgE binding protein, in human mast cells and basophils. Anat. Rec. 242:211. 52. Ohshima, S., S. Kuchen, C. A. Seemayer, D. Kyburz, A. Hirt, S. Klinzing, B. A. Michel, R. E. Gay, F. T. Liu, S. Gay, and M. Neidhart. 2003. Galectin 3 and its binding protein in rheumatoid arthritis. Arthritis Rheum. 48:2788. 53. Nishi, Y., H. Sano, T. Kawashima, T. Okada, T. Kuroda, K. Kikkawa, S. Kawashima, M. Tanabe, T. Goto, Y. Matsuzawa, R. Matsumura, H. Tomioka, F. T. Liu, and K. Shirai. 2007. Role of galectin-3 in human pulmonary fibrosis. Allergol. Int. 56:57. 54. Ochieng, J., M. L. Leite-Browning, and P. Warfield. 1998. Regulation of cellular adhesion to extracellular matrix proteins by galectin-3. Biochem. Biophys. Res. Commun. 246:788. 55. Dong, S., and R. C. Hughes. 1997. Macrophage surface glycoproteins binding to galectin-3 (Mac-2-antigen). Glycoconj. J. 14:267. 56. Hughes, R. C. 2001. Galectins as modulators of cell adhesion. Biochimie 83:667. 57. Demetriou, M., M. Granovsky, S. Quaggin, and J. W. Dennis. 2001. Negative regulation of T-cell activation and autoimmunity by Mgat5 N-glycosylation. Nature 409:733. 58. Wang, L., H. Inohara, K. J. Pienta, and A. Raz. 1995. Galectin-3 is a nuclear matrix protein which binds RNA. Biochem. Biophys. Res. Commun. 217:292. 59. Dagher, S. F., J. L. Wang, and R. J. Patterson. 1995. Identification of galectin-3 as a factor in pre-mRNA splicing. Proc. Natl. Acad. Sci. U. S. A 92:1213. 60. Shimura, T., Y. Takenaka, T. Fukumori, S. Tsutsumi, K. Okada, V. Hogan, A. Kikuchi, H. Kuwano, and A. Raz. 2005. Implication of galectin-3 in Wnt signaling. Cancer Res. 65:3535. 61. Shimura, T., Y. Takenaka, S. Tsutsumi, V. Hogan, A. Kikuchi, and A. Raz. 2004. Galectin-3, a novel binding partner of beta-catenin. Cancer Res. 64:6363. 62. Lin, H. M., R. G. Pestell, A. Raz, and H. R. Kim. 2002. Galectin-3 enhances cyclin D(1) promoter activity through SP1 and a cAMP-responsive element in human breast epithelial cells. Oncogene 21:8001. 63. Cooper, D. N. 2002. Galectinomics: finding themes in complexity. Biochim. Biophys. Acta 1572:209. 64. Ahmad, N., H. J. Gabius, S. Andre, H. Kaltner, S. Sabesan, R. Roy, B. Liu, F. Macaluso, and C. F. Brewer. 2004. Galectin-3 precipitates as a pentamer with synthetic multivalent carbohydrates and forms heterogeneous cross-linked complexes. J. Biol. Chem. 279:10841. 65. Wang, J. L., J. G. Laing, and R. L. Anderson. 1991. Lectins in the cell nucleus. Glycobiology 1:243. 66. Raz, A., G. Pazerini, and P. Carmi. 1989. Identification of the metastasis-associated, galactoside-binding lectin as a chimeric gene product with homology to an IgE-binding protein. Cancer Res. 49:3489. 67. Ochieng, J., R. Fridman, P. Nangia-Makker, D. E. Kleiner, L. A. Liotta, W. G. Stetler-Stevenson, and A. Raz. 1994. Galectin-3 is a novel substrate for human matrix metalloproteinases-2 and -9. Biochemistry 33:14109. 68. Menon, R. P., and R. C. Hughes. 1999. Determinants in the N-terminal domains of galectin-3 for secretion by a novel pathway circumventing the endoplasmic reticulum-Golgi complex. Eur. J. Biochem. 264:569. 69. Mehul, B., and R. C. Hughes. 1997. Plasma membrane targetting, vesicular budding and release of galectin 3 from the cytoplasm of mammalian cells during secretion. J. Cell Sci. 110 ( Pt 10):1169. 70. Sano, H., D. K. Hsu, L. Yu, J. R. Apgar, I. Kuwabara, T. Yamanaka, M. Hirashima, and F. T. Liu. 2000. Human galectin-3 is a novel chemoattractant for monocytes and macrophages. J. Immunol. 165:2156. 71. Yang, R. Y., D. K. Hsu, and F. T. Liu. 1996. Expression of galectin-3 modulates T-cell growth and apoptosis. Proc. Natl. Acad. Sci. U. S. A 93:6737. 72. Akahani, S., P. Nangia-Makker, H. Inohara, H. R. Kim, and A. Raz. 1997. Galectin-3: a novel antiapoptotic molecule with a functional BH1 (NWGR) domain of Bcl-2 family. Cancer Res. 57:5272. 73. Sano, H., D. K. Hsu, J. R. Apgar, L. Yu, B. B. Sharma, I. Kuwabara, S. Izui, and F. T. Liu. 2003. Critical role of galectin-3 in phagocytosis by macrophages. J. Clin. Invest 112:389. 74. Hsu, D. K., R. Y. Yang, Z. Pan, L. Yu, D. R. Salomon, W. P. Fung-Leung, and F. T. Liu. 2000. Targeted disruption of the galectin-3 gene results in attenuated peritoneal inflammatory responses. Am. J. Pathol. 156:1073. 75. Neidhart, M., F. Zaucke, K. R. von, A. Jungel, B. A. Michel, R. E. Gay, and S. Gay. 2005. Galectin-3 is induced in rheumatoid arthritis synovial fibroblasts after adhesion to cartilage oligomeric matrix protein. Ann. Rheum. Dis. 64:419. 76. Mathews, K. P., K. N. Konstantinov, I. Kuwabara, P. N. Hill, D. K. Hsu, B. L. Zuraw, and F. T. Liu. 1995. Evidence for IgG autoantibodies to galectin-3, a beta-galactoside-binding lectin (Mac-2, epsilon binding protein, or carbohydrate binding protein 35) in human serum. J. Clin. Immunol. 15:329. 77. Lim, Y., D. Y. Lee, S. Lee, S. Y. Park, J. Kim, B. Cho, H. Lee, H. Y. Kim, E. Lee, Y. W. Song, and D. I. Jeoung. 2002. Identification of autoantibodies associated with systemic lupus erythematosus. Biochem. Biophys. Res. Commun. 295:119. 78. Marchini, J., D. Cutler, N. Patterson, M. Stephens, E. Eskin, E. Halperin, S. Lin, Z. S. Qin, H. M. Munro, G. R. Abecasis, and P. Donnelly. 2006. A comparison of phasing algorithms for trios and unrelated individuals. Am. J. Hum. Genet. 78:437. 79. Martins, L., S. G. Leoni, C. U. Friguglietti, L. S. Ward, M. A. Kulcsar, and E. T. Kimura. 2006. [Polymorphism on codon 98 of the galectin-3 gene are not associated to benign and malignant thyroid tumors]. Arq Bras. Endocrinol. Metabol. 50:1075. 80. Dabelic, S., S. Supraha, and J. Dumic. 2006. Galectin-3 in macrophage-like cells exposed to immunomodulatory drugs. Biochim. Biophys. Acta 1760:701. 81. Salmon, M., D. Scheel-Toellner, A. P. Huissoon, D. Pilling, N. Shamsadeen, H. Hyde, A. D. D'Angeac, P. A. Bacon, P. Emery, and A. N. Akbar. 1997. Inhibition of T cell apoptosis in the rheumatoid synovium. J. Clin. Invest 99:439. 82. Perlman, H., L. J. Pagliari, C. Georganas, T. Mano, K. Walsh, and R. M. Pope. 1999. FLICE-inhibitory protein expression during macrophage differentiation confers resistance to fas-mediated apoptosis. J. Exp. Med. 190:1679. 83. Jaekell, H. P., A. Trabandt, N. Grobe, and E. Werle. 2006. Anti-dsDNA antibody subtypes and anti-C1q antibodies: toward a more reliable diagnosis and monitoring of systemic lupus erythematosus and lupus nephritis. Lupus 15:335. 84. Forger, F., T. Matthias, M. Oppermann, H. Becker, and K. Helmke. 2004. Clinical significance of anti-dsDNA antibody isotypes: IgG/IgM ratio of anti-dsDNA antibodies as a prognostic marker for lupus nephritis. Lupus 13:36. 85. Stewart, G. A., and P. J. Thompson. 1996. The biochemistry of common aeroallergens. Clin. Exp. Allergy 26:1020. 86. Regan, L. J., J. Dodd, S. H. Barondes, and T. M. Jessell. 1986. Selective expression of endogenous lactose-binding lectins and lactoseries glycoconjugates in subsets of rat sensory neurons. Proc. Natl. Acad. Sci. U. S. A 83:2248. 87. Gritzmacher, C. A., M. W. Robertson, and F. T. Liu. 1988. IgE-binding protein. Subcellular location and gene expression in many murine tissues and cells. J. Immunol. 141:2801. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/29591 | - |
| dc.description.abstract | 半乳糖凝集素-3（Galectin-3, Gal-3）是一種會與β-半乳糖結合的動物性凝集素，由胺基端的重複序列及羧酸端的碳水化合物辨識序列所構成。在免疫反應、細胞週期調控、細胞凋亡、前信使核醣核酸切割、細胞與細胞之間的貼附及細胞與基質貼附的過程中，Gal-3扮演重要的角色。細胞內的Gal-3具有抑制細胞凋亡的能力。缺乏Gal-3的小鼠，發炎反應會有減弱的現象，且腹腔內巨噬細胞的吞噬能力也產生缺陷。先前的報告指出，類風濕性關節炎（Rheumatoid arthritis, RA）病患的血清中，Gal-3表現量有上升的趨勢。
為了探討以Gal-3基因變異作為台灣自體免疫疾病相關遺傳標誌之可能性，我們研究151位類風濕性關節炎與152位全身紅斑性狼瘡（Systemic lupus erythematosus, SLE）病患，針對Gal-3基因（LGALS3）單核苷酸多型性（Single nucleotide polymorphism, SNP）進行調查。結果發現：在151位RA的病人中，+292（rs4652, A>C, Thr98Pro）的C對偶基因型顯著高於控制組（RA: 43.0 %, Control: 33.5 %, p=0.012）。SLE病患群體的LGALS3 +292基因型分布則與控制組之間無顯著差異。比較SLE病患群體中LGALS3 +292對偶基因型攜帶率，發現不帶有+292 C的SLE病患群體（+292 AA），狼瘡性腎炎的發生率明顯高於帶有+292 C的病患（odds ratio=2.22, 95% confidence interval=1.15 – 4.28, p=0.016）。比較RA病人與健康群體的血清Gal-3濃度，並未發現顯著差異；然而LGALS3 +292位點為基因型AA的RA病人，血清Gal-3的濃度（13.1±5.6 ng/mL）明顯高於+292基因型CC的病人（9.1±3.2 ng/mL）（p=0.011）。以西方墨點法分析正常人巨噬細胞內Gal-3的含量，發現位點+292 CC基因型的巨噬細胞內Gal-3含量高於+292 AA基因型之個體。分析SLE患者血清， 20.6 % （30/146）出現抗Gal-3自體抗體，並與中樞神經病變具有相關性（odds ratio=2.67, 95% CI=1.02 – 6.99, p=0.046）。 本研究發現LGALS3 +292位點之SNP與RA罹病以及SLE病患之狼瘡腎病變相關。LGLAS3 +292之變異可能與Gal-3蛋白的分泌及細胞內堆積有關。另外，抗Gal-3自體抗體的存在與SLE患者發生中樞神經病變具相關性，但與LGALS3 +292位點的基因變異無關。因此LGALS3 +292位點變異應有潛力躋身為國人RA的基因標記之ㄧ。進一步探討LGALS3 +292位點所造成的蛋白分泌或功能差異，將有助於解析Gal-3在自體免疫疾病中可能扮演之角色。 | zh_TW |
| dc.description.provenance | Made available in DSpace on 2021-06-13T01:11:26Z (GMT). No. of bitstreams: 1 ntu-96-R94424025-1.pdf: 813784 bytes, checksum: 4b475bac5ec98dccabf27037f3388f77 (MD5) Previous issue date: 2007 | en |
| dc.description.tableofcontents | 中文摘要 I
英文摘要 III 第一章 緒論 1 第一節 類風濕性關節的簡介與相關文獻探討 1 第二節 全身紅斑性狼瘡的簡介與相關文獻探討 5 第三節 半乳糖凝集素-3（Galectin-3）的簡介與相關文獻探討 9 第四節 類風濕性關節炎與半乳糖凝集素-3相關文獻探討 15 第五節 全身紅斑性狼瘡與半乳糖凝集素-3相關文獻探討 16 第六節 研究目的 17 第二章 材料與方法 18 第一節 材料 18 1.1 試藥 1.2 試劑组 1.3 各式溶液 1.3-1 去氧核醣核酸萃取（DNA extraction） 1.3-2 酵素連結免疫吸附分析（ELISA） 1.3-3 人類巨噬細胞培養 1.3-4 細胞蛋白質萃取 1.3-5 十二烷基磺酸鈉聚丙烯酰胺凝膠電泳（SDS-PAGE） 1.3-6 西方墨點法 1.4 各式抗體 1.5 重要儀器及相關耗材 第二節 實驗方法 27 2.1 檢體收集（Sample collection） 2.2 檢體DNA之製備與基因型分析 2.2-1 去氧核醣核酸萃取（DNA extraction） 2.2-2 聚合酶連鎖反應（PCR） 2.2-3 序列特異性寡核苷酸探針雜交（SSOPH） 2.2-4 限制酶片段長度多型性（RFLP） 2.3 酵素連結免疫吸附分析（ELISA） 2.3-1定量類風濕性關節炎患者血清半乳糖凝集素-3濃度 2.3-2偵測全身紅斑性狼瘡患者血清抗半乳糖凝集素-3自體抗體 2.4 以西方墨點法偵測巨噬細胞內半乳糖凝集素-3之表現量 2.4-1人類巨噬細胞培養 2.4-2細胞蛋白質萃取 2.4-3西方墨點法 2.5 西方墨點法確認SLE病患血清抗半乳糖凝集素-3自體抗體之存在 2.6 統計方法（Statistic methods） 第三章 結果 39 第一節 自體免疫疾病病患之半乳糖凝集素-3基因型分析 39 1.1 Gal-3基因位點+191（A→C, His64Pro）之SNP變化 與全身紅斑性狼瘡（SLE）或類風濕性關節炎（RA）罹病無顯著關聯 1.2 Gal-3基因位點+292(A→C, Thr98Pro)之變異會影響類風濕 性關節炎（RA）罹病率 1.3 Gal-3基因位點+191與+292之連鎖性分析：+191 C / +292 C 半套體（Haplotype）與RA罹病具正相關 第二節 半乳糖凝集素-3基因型與SLE病患臨床症狀分析 45 2.1 Gal-3基因位點+292之基因型與SLE病患臨床症狀之分析─ 位點+292基因型與狼瘡腎病變具有相關性 2.2 Gal-3基因位點+292對偶基因型攜帶率與臨床症狀之分析─ 具有+292 C對偶基因型之SLE患者出現狼瘡腎病變 的比例顯著下降 第三節 類風濕性關節炎（RA）患者血清之半乳糖凝集素-3與 其胺基酸變異之相關性分析─具98Pro型有較高的血清 半乳糖凝集素-3 48 第四節 巨噬細胞內半乳糖凝集素-3之堆積與其胺基酸變異 （98Thr→98Pro）具有正相關性 50 第五節 偵測全身紅斑性狼瘡（SLE）患者血清抗半乳糖凝集素-3 自體抗體（Anti-galectin-3 autoantibody）以及與基因型 及臨床症狀之相關性 52 5.1 抗Gal-3自體抗體之有無與Gal-3基因位點+292基因型並無關聯性 5.2 抗Gal-3自體抗體之有無與臨床症狀之關聯性分析 第四章 討論 55 第五章 參考文獻 62 圖目錄 圖一、利用聚合酶連鎖反應（PCR）增幅Gal-3基因之第三、第五 及第六外顯子（Exon）及核酸定序結果 72 圖二、利用限制酶片段長度多型性（RFLP）及序列特異寡核苷探針 雜交法（SSOPH）針對Gal-3基因位點+191（Codon 64）及 +292（Codon 98）進行基因型分析 73 圖三、酵素連結免疫吸附分析定量血清半乳糖凝集素-3 74 圖四、比較周邊血液單核細胞內半乳糖凝集素-3之表現 75 圖五、以西方墨點法確認血清抗半乳糖凝集素-3自體抗體 76 表目錄 表一、LGALS3基因型分析實驗使用之核酸引子及特異性寡核酸探針 序列 77 表二、實驗檢體之年齡與性別分佈 78 表三、少量國人DNA樣本之LGALS3單核苷酸多型性（SNPs）分析 79 表四、LGALS3單核苷酸多型性基因型頻率分佈 80 表五、LGALS3單核苷酸多型性之連鎖分析 82 表六、全身紅斑性狼瘡病人臨床症狀與LGALS3基因型分析 84 表七、全身紅斑性狼瘡病人之血清抗Gal-3自體抗體 （Anti-galectin-3 autoantibody）與位點+292之基因型及 其臨床症狀進行關聯性分析 86 附錄表、圖目錄 附錄一、SLEDAI-2K （全身性紅斑狼瘡活性指標-2K） 88 附錄二、人類半乳糖凝集素-3基因（LGALS3）之單核苷酸多型性 89 | |
| dc.language.iso | zh-TW | |
| dc.subject | 風濕性關節炎 RA | zh_TW |
| dc.subject | 全身紅斑性狼 | zh_TW |
| dc.subject | 瘡 SLE | zh_TW |
| dc.subject | 半乳糖凝集素-3 Galectin-3 | zh_TW |
| dc.subject | 單核苷 | zh_TW |
| dc.subject | 位點多型性 SNP | zh_TW |
| dc.subject | 台灣 | zh_TW |
| dc.subject | Systemic lupus erythematosus SLE | en |
| dc.subject | Taiwan | en |
| dc.subject | Single nucleotide polymorphism SNP | en |
| dc.subject | Galectin-3 | en |
| dc.subject | Rheumatoid arthritis RA | en |
| dc.title | 半乳糖凝集素-3基因多型性與台灣地區類風濕性關節炎之發生及紅斑性狼瘡腎病變之探討 | zh_TW |
| dc.title | Investigating genetic polymorphisms at Galectin-3 gene (LGALS3) in the rheumatoid arthritis susceptibility and lupus-associated nephritis in Taiwanese population | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 95-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 許秉寧,孫光蕙,楊雅倩 | |
| dc.subject.keyword | 全身紅斑性狼,瘡 SLE,類,風濕性關節炎 RA,半乳糖凝集素-3 Galectin-3,單核苷,位點多型性 SNP,台灣, | zh_TW |
| dc.subject.keyword | Systemic lupus erythematosus SLE,Rheumatoid arthritis RA,Galectin-3,Single nucleotide polymorphism SNP,Taiwan, | en |
| dc.relation.page | 89 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2007-07-20 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 醫學檢驗暨生物技術學研究所 | zh_TW |
| 顯示於系所單位： | 醫學檢驗暨生物技術學系 | |
文件中的檔案：
| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| ntu-96-1.pdf 未授權公開取用 | 794.71 kB | Adobe PDF |
系統中的文件，除了特別指名其著作權條款之外，均受到著作權保護，並且保留所有的權利。