研究生: |
劉國保 Liu Kuo-Pao |
---|---|
論文名稱: |
RAS系統和TGF-β1的基因多型性與原發性VUR疾病發生和腎病進行的相關性研究 Study of Association of RAS and TGF-β1 Gene Polymorphisms with Primary VUR Development and Progression |
指導教授: |
李桂楨
Lee, Guey-Jen |
學位類別: |
碩士 Master |
系所名稱: |
生命科學系 Department of Life Science |
論文出版年: | 2003 |
畢業學年度: | 91 |
語文別: | 中文 |
中文關鍵詞: | 膀胱輸尿管逆流 、腎素-血管收縮素系統 、基因多型性 |
論文種類: | 學術論文 |
相關次數: | 點閱:210 下載:8 |
分享至: |
查詢本校圖書館目錄 查詢臺灣博碩士論文知識加值系統 勘誤回報 |
膀胱輸尿管逆流(VUR)為常見的小兒泌尿道疾病,部分病患會進行至末期腎病(ESRD)。VUR的發生與家族遺傳具高度相關性,且患者間的腎病進行差異很大。RAS系統和TGF-β1參與了泌尿系統的發育過程,且可能與腎臟疾病的病程進行相關。本研究以PCR及直接定序、限制酶切割或單股核酸構形多型性分析等技術,檢視了16位末期腎病與58位非末期腎病之原發性VUR病童和117位正常人,其RAS系統相關基因的AGT、ACE、AT1R及TGF-β1基因共25個多型性,和原發性VUR疾病發生及腎病進行的相關性。結果發現AGT基因之C-18T和TGF-β1基因之A-880G、G-800A、R25P、T263I等多型性並不存在於台灣族群中,並於ACE基因上檢視到未曾正式報導的A-3692C多型性。在族群遺傳分析方面,正常人族群中各多型性基因座的遺傳情形均處於哈溫平衡。AGT基因之C-532T與G-217A、A-20C與T174M、G-6A與M235T多型性間呈現強烈的連鎖不平衡現象;ACE基因啟動子上T-5491C、A-5466C、T-3892C、A-3692C、A-240T與介入子16內的I/D多型性間亦呈現非逢機的組合,顯示基因內重組率相當低;AT1R基因之A-1138T、T-810A、T-713G、C-521T、A-214C/G-213C及A-153G多型性間亦呈現強烈的連鎖不平衡。若針對原發性VUR病患與正常人族群之多型性對偶基因頻率進行相關性分析,僅TGF-β1基因之C-509T多型性具顯著性差異,其中對偶基因T與原發性VUR疾病發生有關。若以末期腎病的有無將原發性VUR患者分為二群時,則ACE基因上連鎖之多型性與腎病進行相關,其中T-A-T-A-A-I之單套型形式可視為病程惡化的危險因子。在多型性啟動子的轉錄活性分析方面,本研究構築了RAS系統相關基因之多型性單套型啟動子重組質體,以報導基因luciferase於293細胞株中進行體外基因表現。結果顯示包含A-240T及T-93C多型性之1.2 kb長(-1207 ~ +4)的ACE基因啟動子片段,與包含A-1138T、T-810A、T-713G、C-521T、A-214C/G-213C及A-153G多型性之1.4 kb長(-1332 ~ +45)的AT1R基因啟動子片段,均不影響報導基因的表現量;而包含C-532T、G-217A、G-152A、A-20C及G-6A多型性之0.7 kb長(-567 ~ +116)的AGT基因啟動子片段,含對偶基因-152G的啟動子轉錄活性達顯著差異,其中對偶基因G較A約有2.4倍高的轉錄活性。
Vesicoureteral reflux (VUR) is a common pediatric disease that may lead to severe end-stage renal disease (ESRD) in part of patients. The development of VUR is highly familial inherited and the disease progression is variable. The renin-angiotensin system (RAS) and transforming growth factor-b1 (TGF-b1) involve in the development of urinary system and may also be the potential candidate prognostic factors in the progression of ESRD. In this study, the RAS related angiotensinogen (AGT), angiotensin-converting enzyme (ACE), and angiotensin II type 1 receptor (AT1R) as well as TGF-b1 gene polymorphisms were investigated for association with VUR susceptibility and progression in 74 Taiwanese children, including 16 with ESRD, and 117 normal controls. By polymerase chain reaction and directing sequencing, restriction enzyme digestion, or single strand conformation polymorphism analysis, a total of 25 polymorphisms within the AGT, ACE, AT1R, and TGF-b1 genes were studied. The novel ACE A-3692C was not formally reported, and no TGF-b1 A-880G, G-800A, R25P and T263I polymorphisms were detected. All the polymorphisms examined were in Hardy-Weinberg equilibrium. In the AGT gene, strong linkage disequilibrium between C-532T and G-217A, A-20C and T174M, A-6G and M235T were observed. The strong non-random association among the ACE gene T-5491C, A-5466C, T-3892C, A-3692C, A-240T, and Alu I/D polymorphisms spanning promoter to intron 16 suggests low levels of intragenic recombination within the ACE gene. Similar strong linkage disequilibrium was also seen in the AT1R gene A-1138T, T-810A, T-713G, C-521T, A-214C/G-213C, and A-153G polymorphisms. A statistically significant difference between primary VUR patients and normal controls was observed at the TGF-b1 gene -509 site, with T allele associated with primary VUR development. Furthermore, a significant allele association with ESRD was observed for the ACE loci, with the linked T-A-T-A-A-I haplotype as a risk factor for primary VUR progression. To assess the effect of polymorphism on gene expression, fragments containing the polymorphic haplotypes were fused to firefly luciferase reporter construct and transiently expressed in 293 cells. Within the 1.2 kb ACE and 1.4 kb AT1R promoter fragments, no appreciable effect on the gene expression was observed for the linked ACE A-240T and T-93C as well as the linked AT1R polymorphisms. However, reporter construct containing the AGT -152 G allele drove 2.4 times transcriptional activity compared with the -152 A allele.
1. Cotran, R., Kumar, V. and Robbins, S. (1989) Robbins pathologic basis of disease. W.B. Saunders Company.
2. Dillon, M.J. and Goonasekera, C.D. (1998) Reflux nephropathy. J Am Soc Nephrol, 9, 2377-83.
3. Kamil, E.S. (2000) Recent advances in the understanding and management of primary vesicoureteral reflux and reflux nephropathy. Curr Opin Nephrol Hypertens, 9, 139-42.
4. Devriendt, K., Groenen, P., Van Esch, H., van Dijck, M., Van de Ven, W., Fryns, J.P. and Proesmans, W. (1998) Vesico-ureteral reflux: a genetic condition? Eur J Pediatr, 157, 265-71.
5. Eccles, M.R., Bailey, R.R., Abbott, G.D. and Sullivan, M.J. (1996) Unravelling the genetics of vesicoureteric reflux: a common familial disorder. Hum Mol Genet, 5 Spec No, 1425-9.
6. Kaefer, M., Curran, M., Treves, S.T., Bauer, S., Hendren, W.H., Peters, C.A., Atala, A., Diamond, D. and Retik, A. (2000) Sibling vesicoureteral reflux in multiple gestation births. Pediatrics, 105, 800-4.
7. Noe, H.N. (1988) The relationship of sibling reflux to index patient dysfunctional voiding. J Urol, 140, 119-20.
8. de Vargas, A., Evans, K., Ransley, P., Rosenberg, A.R., Rothwell, D., Sherwood, T., Williams, D.I., Barratt, T.M. and Carter, C.O. (1978) A family study of vesicoureteric reflux. J Med Genet, 15, 85-96.
9. Jerkins, G.R. and Noe, H.N. (1982) Familial vesicoureteral reflux: a prospective study. J Urol, 128, 774-8.
10. Middleton, G.W., Howards, S.S. and Gillenwater, J.Y. (1975) Sex-linked familial reflux. J Urol, 114, 36-9.
11. Chertin, B., Rolle, U., Cascio, S., McDermot, M., O'Briain, S., Farkas, A. and Puri, P. (2002) Upregulation of angiotensin II receptors in reflux nephropathy. J Pediatr Surg, 37, 251-5.
12. Andriole, V.T. (1985) The role of Tamm-Horsfall protein in the pathogenesis of reflux nephropathy and chronic pyelonephritis. Yale J Biol Med, 58, 91-100.
13. Reid, I.A., Morris, B.J. and Ganong, W.F. (1978) The renin-angiotensin system. Annu Rev Physiol, 40, 377-410.
14. Skeggs, L., Dorer, F., Levine, M., Lentz, K. and Kahn, J. (1980) In "The Renin-angiotensin system", Johnson JA, Anderson RR, Eds. In. Plenum, New York., pp. 1-27.
15. Kurokawa, K. (1998) Tubuloglomerular feedback: its physiological and pathophysiological significance. Kidney Int Suppl, 54, S71-4.
16. Kageyama, R., Ohkubo, H. and Nakanishi, S. (1984) Primary structure of human preangiotensinogen deduced from the cloned cDNA sequence. Biochemistry, 23, 3603-9.
17. Givertz, M.M. (2001) Manipulation of the renin-angiotensin system. Circulation, 104, E14-8.
18. Sigmund, C.D. (2001) Genetic manipulation of the renin-angiotensin system in the kidney. Acta Physiol Scand, 173, 67-73.
19. Ehlers, M.R. and Riordan, J.F. (1989) Angiotensin-converting enzyme: new concepts concerning its biological role. Biochemistry, 28, 5311-8.
20. Gaillard, I., Clauser, E. and Corvol, P. (1989) Structure of human angiotensinogen gene. DNA, 8, 87-99.
21. Fukamizu, A., Takahashi, S., Seo, M.S., Tada, M., Tanimoto, K., Uehara, S. and Murakami, K. (1990) Structure and expression of the human angiotensinogen gene: identification of a unique and highly active promoter. J Biol Chem, 265, 7576-82.
22. Gimenez-Roqueplo, A.P., Celerier, J., Lucarelli, G., Corvol, P. and Jeunemaitre, X. (1998) Role of N-glycosylation in human angiotensinogen. J Biol Chem, 273, 21232-8.
23. Campbell, D.J. and Habener, J.F. (1986) Angiotensinogen gene is expressed and differentially regulated in multiple tissues of the rat. J Clin Invest, 78, 31-9.
24. Campbell, D.J. and Habener, J.F. (1987) Cellular localization of angiotensinogen gene expression in brown adipose tissue and mesentery: quantification of messenger ribonucleic acid abundance using hybridization in situ. Endocrinology, 121, 1616-26.
25. Jain, S., Tang, X., Narayanan, C.S., Agarwal, Y., Peterson, S.M., Brown, C.D., Ott, J. and Kumar, A. (2002) Angiotensinogen gene polymorphism at -217 affects basal promoter activity and is associated with hypertension in African-Americans. J Biol Chem, 277, 36889-96.
26. Sato, N., Katsuya, T., Nakagawa, T., Ishikawa, K., Fu, Y., Asai, T., Fukuda, M., Suzuki, F., Nakamura, Y., Higaki, J. and Ogihara, T. (2000) Nine polymorphisms of angiotensinogen gene in the susceptibility to essential hypertension. Life Sci, 68, 259-72.
27. Paillard, F., Chansel, D., Brand, E., Benetos, A., Thomas, F., Czekalski, S., Ardaillou, R. and Soubrier, F. (1999) Genotype-phenotype relationships for the renin-angiotensin-aldosterone system in a normal population. Hypertension, 34, 423-9.
28. Hata, A., Namikawa, C., Sasaki, M., Sato, K., Nakamura, T., Tamura, K. and Lalouel, J.M. (1994) Angiotensinogen as a risk factor for essential hypertension in Japan. J Clin Invest, 93, 1285-7.
29. Jeunemaitre, X., Soubrier, F., Kotelevtsev, Y.V., Lifton, R.P., Williams, C.S., Charru, A., Hunt, S.C., Hopkins, P.N., Williams, R.R., Lalouel, J.M. and et al. (1992) Molecular basis of human hypertension: role of angiotensinogen. Cell, 71, 169-80.
30. Caulfield, M., Lavender, P., Farrall, M., Munroe, P., Lawson, M., Turner, P. and Clark, A.J. (1994) Linkage of the angiotensinogen gene to essential hypertension. N Engl J Med, 330, 1629-33.
31. Caulfield, M., Lavender, P., Newell-Price, J., Farrall, M., Kamdar, S., Daniel, H., Lawson, M., De Freitas, P., Fogarty, P. and Clark, A.J. (1995) Linkage of the angiotensinogen gene locus to human essential hypertension in African Caribbeans. J Clin Invest, 96, 687-92.
32. Morgan, L., Crawshaw, S., Baker, P.N., Pipkin, F.B. and Kalsheker, N. (2000) Polymorphism in oestrogen response element associated with variation in plasma angiotensinogen concentrations in healthy pregnant women. J Hypertens, 18, 553-7.
33. Jeunemaitre, X., Inoue, I., Williams, C., Charru, A., Tichet, J., Powers, M., Sharma, A.M., Gimenez-Roqueplo, A.P., Hata, A., Corvol, P. and Lalouel, J.M. (1997) Haplotypes of angiotensinogen in essential hypertension. Am J Hum Genet, 60, 1448-60.
34. Inoue, I., Nakajima, T., Williams, C.S., Quackenbush, J., Puryear, R., Powers, M., Cheng, T., Ludwig, E.H., Sharma, A.M., Hata, A., Jeunemaitre, X. and Lalouel, J.M. (1997) A nucleotide substitution in the promoter of human angiotensinogen is associated with essential hypertension and affects basal transcription in vitro. J Clin Invest, 99, 1786-97.
35. Zhao, Y.Y., Zhou, J., Narayanan, C.S., Cui, Y. and Kumar, A. (1999) Role of C/A polymorphism at -20 on the expression of human angiotensinogen gene. Hypertension, 33, 108-15.
36. Yanai, K., Saito, T., Hirota, K., Kobayashi, H., Murakami, K. and Fukamizu, A. (1997) Molecular variation of the human angiotensinogen core promoter element located between the TATA box and transcription initiation site affects its transcriptional activity. J Biol Chem, 272, 30558-62.
37. Hubert, C., Houot, A.M., Corvol, P. and Soubrier, F. (1991) Structure of the angiotensin I-converting enzyme gene. Two alternate promoters correspond to evolutionary steps of a duplicated gene. J Biol Chem, 266, 15377-83.
38. Krulewitz, A.H., Baur, W.E. and Fanburg, B.L. (1984) Hormonal influence on endothelial cell angiotensin-converting enzyme activity. Am J Physiol, 247, C163-8.
39. Velletri, P.A., Aquilano, D.R., Bruckwick, E., Tsai-Morris, C.H., Dufau, M.L. and Lovenberg, W. (1985) Endocrinological control and cellular localization of rat testicular angiotensin-converting enzyme (EC 3.4.15.1). Endocrinology, 116, 2516-22.
40. Lattion, A.L., Soubrier, F., Allegrini, J., Hubert, C., Corvol, P. and Alhenc-Gelas, F. (1989) The testicular transcript of the angiotensin I-converting enzyme encodes for the ancestral, non-duplicated form of the enzyme. FEBS Lett, 252, 99-104.
41. Sadhukhan, R., Sen, G.C., Ramchandran, R. and Sen, I. (1998) The distal ectodomain of angiotensin-converting enzyme regulates its cleavage-secretion from the cell surface. Proc Natl Acad Sci U S A, 95, 138-43.
42. Esther, C.R., Marino, E.M., Howard, T.E., Machaud, A., Corvol, P., Capecchi, M.R. and Bernstein, K.E. (1997) The critical role of tissue angiotensin-converting enzyme as revealed by gene targeting in mice. J Clin Invest, 99, 2375-85.
43. Soubrier, F., Alhenc-Gelas, F., Hubert, C., Allegrini, J., John, M., Tregear, G. and Corvol, P. (1988) Two putative active centers in human angiotensin I-converting enzyme revealed by molecular cloning. Proc Natl Acad Sci U S A, 85, 9386-90.
44. Turner, A.J. and Hooper, N.M. (2002) The angiotensin-converting enzyme gene family: genomics and pharmacology. Trends Pharmacol Sci, 23, 177-83.
45. Ehlers, M.R., Fox, E.A., Strydom, D.J. and Riordan, J.F. (1989) Molecular cloning of human testicular angiotensin-converting enzyme: the testis isozyme is identical to the C-terminal half of endothelial angiotensin-converting enzyme. Proc Natl Acad Sci U S A, 86, 7741-5.
46. Hinman, L.M., Stevens, C., Matthay, R.A., Bernard, J. and Gee, L. (1979) Angiotensin convertase activities in human alveolar macrophages: effects of cigarette smoking and sarcoidosis. Science, 205, 202-3.
47. Erdos, E.G. and Skidgel, R.A. (1987) The angiotensin I-converting enzyme. Lab Invest, 56, 345-8.
48. Payan, D.G. (1989) Neuropeptides and inflammation: the role of substance P. Annu Rev Med, 40, 341-52.
49. Rigat, B., Hubert, C., Alhenc-Gelas, F., Cambien, F., Corvol, P. and Soubrier, F. (1990) An insertion/deletion polymorphism in the angiotensin I-converting enzyme gene accounting for half the variance of serum enzyme levels. J Clin Invest, 86, 1343-6.
50. Hunley, T.E., Julian, B.A., Phillips, J.A., 3rd, Summar, M.L., Yoshida, H., Horn, R.G., Brown, N.J., Fogo, A., Ichikawa, I. and Kon, V. (1996) Angiotensin converting enzyme gene polymorphism: potential silencer motif and impact on progression in IgA nephropathy. Kidney Int, 49, 571-7.
51. Evans, A.E., Poirier, O., Kee, F., Lecerf, L., McCrum, E., Falconer, T., Crane, J., O'Rourke, D.F. and Cambien, F. (1994) Polymorphisms of the angiotensin-converting-enzyme gene in subjects who die from coronary heart disease. Q J Med, 87, 211-4.
52. Hingorani, A.D., Jia, H., Stevens, P.A., Hopper, R., Dickerson, J.E. and Brown, M.J. (1995) Renin-angiotensin system gene polymorphisms influence blood pressure and the response to angiotensin converting enzyme inhibition. J Hypertens, 13, 1602-9.
53. O'Donnell, C.J., Lindpaintner, K., Larson, M.G., Rao, V.S., Ordovas, J.M., Schaefer, E.J., Myers, R.H. and Levy, D. (1998) Evidence for association and genetic linkage of the angiotensin-converting enzyme locus with hypertension and blood pressure in men but not women in the Framingham Heart Study. Circulation, 97, 1766-72.
54. O'Malley, J.P., Maslen, C.L. and Illingworth, D.R. (1998) Angiotensin-converting enzyme DD genotype and cardiovascular disease in heterozygous familial hypercholesterolemia. Circulation, 97, 1780-3.
55. Perticone, F., Maio, R., Cosco, C., Ceravolo, R., Iacopino, S., Chello, M., Mastroroberto, P., Tramontano, D. and Mattioli, P.L. (1999) Hypertensive left ventricular remodeling and ACE-gene polymorphism. Cardiovasc Res, 43, 192-9.
56. Yoshida, H., Mitarai, T., Kawamura, T., Kitajima, T., Miyazaki, Y., Nagasawa, R., Kawaguchi, Y., Kubo, H., Ichikawa, I. and Sakai, O. (1995) Role of the deletion of polymorphism of the angiotensin converting enzyme gene in the progression and therapeutic responsiveness of IgA nephropathy. J Clin Invest, 96, 2162-9.
57. Baboolal, K., Ravine, D., Daniels, J., Williams, N., Holmans, P., Coles, G.A. and Williams, J.D. (1997) Association of the angiotensin I converting enzyme gene deletion polymorphism with early onset of ESRF in PKD1 adult polycystic kidney disease. Kidney Int, 52, 607-13.
58. Lee, D.Y., Kim, W., Kang, S.K., Koh, G.Y. and Park, S.K. (1997) Angiotensin-converting enzyme gene polymorphism in patients with minimal-change nephrotic syndrome and focal segmental glomerulosclerosis. Nephron, 77, 471-3.
59. Frishberg, Y., Becker-Cohen, R., Halle, D., Feigin, E., Eisenstein, B., Halevy, R., Lotan, D., Juabeh, I., Ish-Shalom, N., Magen, D., Shvil, Y., Sinai-Treiman, L. and Drukker, A. (1998) Genetic polymorphisms of the renin-angiotensin system and the outcome of focal segmental glomerulosclerosis in children. Kidney Int, 54, 1843-9.
60. Villard, E., Tiret, L., Visvikis, S., Rakotovao, R., Cambien, F. and Soubrier, F. (1996) Identification of new polymorphisms of the angiotensin I-converting enzyme (ACE) gene, and study of their relationship to plasma ACE levels by two-QTL segregation-linkage analysis. Am J Hum Genet, 58, 1268-78.
61. Keavney, B., McKenzie, C.A., Connell, J.M., Julier, C., Ratcliffe, P.J., Sobel, E., Lathrop, M. and Farrall, M. (1998) Measured haplotype analysis of the angiotensin-I converting enzyme gene. Hum Mol Genet, 7, 1745-51.
62. Nakamura, T., Suehiro, T., Wang, K., Shiinoki, T., Kumon, Y., Inoue, M., Morita, T., Tanimoto, K. and Hashimoto, K. (2000) Polymorphisms in the upstream region of angiotensin 1-converting enzyme (ACE) gene regulation ace promoter activity. XIIth International Symposium on Atherosclerosis (Stockholm, Sweden), TuP5:W15.
63. Rieder, M.J., Taylor, S.L., Clark, A.G. and Nickerson, D.A. (1999) Sequence variation in the human angiotensin converting enzyme. Nat Genet, 22, 59-62.
64. Ardaillou, R. (1999) Angiotensin II receptors. J Am Soc Nephrol, 10 Suppl 11, S30-9.
65. Allen, A.M., Zhuo, J. and Mendelsohn, F.A. (1999) Localization of angiotensin AT1 and AT2 receptors. J Am Soc Nephrol, 10 Suppl 11, S23-9.
66. Furuta, H., Guo, D.F. and Inagami, T. (1992) Molecular cloning and sequencing of the gene encoding human angiotensin II type 1 receptor. Biochem Biophys Res Commun, 183, 8-13.
67. Guo, D.F., Furuta, H., Mizukoshi, M. and Inagami, T. (1994) The genomic organization of human angiotensin II type 1 receptor. Biochem Biophys Res Commun, 200, 313-9.
68. Su, B., Martin, M.M., Beason, K.B., Miller, P.J. and Elton, T.S. (1994) The genomic organization and functional analysis of the promoter for the human angiotensin II type 1 receptor. Biochem Biophys Res Commun, 204, 1039-46.
69. Murasawa, S., Matsubara, H., Urakami, M. and Inada, M. (1993) Regulatory elements that mediate expression of the gene for the angiotensin II type 1a receptor for the rat. J Biol Chem, 268, 26996-7003.
70. Takeuchi, K., Alexander, R.W., Nakamura, Y., Tsujino, T. and Murphy, T.J. (1993) Molecular structure and transcriptional function of the rat vascular AT1a angiotensin receptor gene. Circ Res, 73, 612-21.
71. Hunyady, L., Balla, T. and Catt, K.J. (1996) The ligand binding site of the angiotensin AT1 receptor. Trends Pharmacol Sci, 17, 135-40.
72. Nishimura, H. (2001) Angiotensin receptors--evolutionary overview and perspectives. Comp Biochem Physiol A Mol Integr Physiol, 128, 11-30.
73. Erdmann, J., Riedel, K., Rohde, K., Folgmann, I., Wienker, T., Fleck, E. and Regitz-Zagrosek, V. (1999) Characterization of polymorphisms in the promoter of the human angiotensin II subtype 1 (AT1) receptor gene. Ann Hum Genet, 63 ( Pt 4), 369-74.
74. Tiret, L., Bonnardeaux, A., Poirier, O., Ricard, S., Marques-Vidal, P., Evans, A., Arveiler, D., Luc, G., Kee, F., Ducimetiere, P. and et al. (1994) Synergistic effects of angiotensin-converting enzyme and angiotensin-II type 1 receptor gene polymorphisms on risk of myocardial infarction. Lancet, 344, 910-3.
75. Buraczynska, M., Ksiazek, P., Zaluska, W., Spasiewicz, D., Nowicka, T. and Ksiazek, A. (2002) Angiotensin II type 1 receptor gene polymorphism in end-stage renal disease. Nephron, 92, 51-5.
76. Zhang, X., Erdmann, J., Regitz-Zagrosek, V., Kurzinger, S., Hense, H.W. and Schunkert, H. (2000) Evaluation of three polymorphisms in the promoter region of the angiotensin II type I receptor gene. J Hypertens, 18, 267-72.
77. Takayanagi, R., Ohnaka, K., Sakai, Y., Ikuyama, S. and Nawata, H. (1994) Molecular cloning and characterization of the promoter for human type-1 angiotensin II receptor gene. Biochem Biophys Res Commun, 200, 1264-70.
78. Grainger, D.J., Heathcote, K., Chiano, M., Snieder, H., Kemp, P.R., Metcalfe, J.C., Carter, N.D. and Spector, T.D. (1999) Genetic control of the circulating concentration of transforming growth factor type beta1. Hum Mol Genet, 8, 93-7.
79. Derynck, R., Rhee, L., Chen, E.Y. and Van Tilburg, A. (1987) Intron-exon structure of the human transforming growth factor-beta precursor gene. Nucleic Acids Res, 15, 3188-9.
80. Kim, S.J., Glick, A., Sporn, M.B. and Roberts, A.B. (1989) Characterization of the promoter region of the human transforming growth factor-beta 1 gene. J Biol Chem, 264, 402-8.
81. Derynck, R., Jarrett, J.A., Chen, E.Y., Eaton, D.H., Bell, J.R., Assoian, R.K., Roberts, A.B., Sporn, M.B. and Goeddel, D.V. (1985) Human transforming growth factor-beta complementary DNA sequence and expression in normal and transformed cells. Nature, 316, 701-5.
82. Hutchinson, I.V. (1999) The role of transforming growth factor-beta in transplant rejection. Transplant Proc, 31, 9S-13S.
83. Cambien, F., Ricard, S., Troesch, A., Mallet, C., Generenaz, L., Evans, A., Arveiler, D., Luc, G., Ruidavets, J.B. and Poirier, O. (1996) Polymorphisms of the transforming growth factor-beta 1 gene in relation to myocardial infarction and blood pressure: the Etude Cas-Temoin de l'Infarctus du Myocarde (ECTIM) Study. Hypertension, 28, 881-7.
84. Langdahl, B.L., Knudsen, J.Y., Jensen, H.K., Gregersen, N. and Eriksen, E.F. (1997) A sequence variation: 713-8delC in the transforming growth factor-beta 1 gene has higher prevalence in osteoporotic women than in normal women and is associated with very low bone mass in osteoporotic women and increased bone turnover in both osteoporotic and normal women. Bone, 20, 289-94.
85. Kim, S.J., Wagner, S., Liu, F., O'Reilly, M.A., Robbins, P.D. and Green, M.R. (1992) Retinoblastoma gene product activates expression of the human TGF-beta 2 gene through transcription factor ATF-2. Nature, 358, 331-4.
86. Hobbs, K., Negri, J., Klinnert, M., Rosenwasser, L.J. and Borish, L. (1998) Interleukin-10 and transforming growth factor-beta promoter polymorphisms in allergies and asthma. Am J Respir Crit Care Med, 158, 1958-62.
87. Luedecking, E.K., DeKosky, S.T., Mehdi, H., Ganguli, M. and Kamboh, M.I. (2000) Analysis of genetic polymorphisms in the transforming growth factor-beta1 gene and the risk of Alzheimer's disease. Hum Genet, 106, 565-9.
88. Wood, N.A., Thomson, S.C., Smith, R.M. and Bidwell, J.L. (2000) Identification of human TGF-beta1 signal (leader) sequence polymorphisms by PCR-RFLP. J Immunol Methods, 234, 117-22.
89. Awad, M.R., El-Gamel, A., Hasleton, P., Turner, D.M., Sinnott, P.J. and Hutchinson, I.V. (1998) Genotypic variation in the transforming growth factor-beta1 gene: association with transforming growth factor-beta1 production, fibrotic lung disease, and graft fibrosis after lung transplantation. Transplantation, 66, 1014-20.
90. Shirai, Y., Kawata, S., Ito, N., Tamura, S., Takaishi, K., Kiso, S., Tsushima, H. and Matsuzawa, Y. (1992) Elevated levels of plasma transforming growth factor-beta in patients with hepatocellular carcinoma. Jpn J Cancer Res, 83, 676-9.
91. Anscher, M.S., Peters, W.P., Reisenbichler, H., Petros, W.P. and Jirtle, R.L. (1993) Transforming growth factor beta as a predictor of liver and lung fibrosis after autologous bone marrow transplantation for advanced breast cancer. N Engl J Med, 328, 1592-8.
92. Grainger, D.J., Kemp, P.R., Metcalfe, J.C., Liu, A.C., Lawn, R.M., Williams, N.R., Grace, A.A., Schofield, P.M. and Chauhan, A. (1995) The serum concentration of active transforming growth factor-beta is severely depressed in advanced atherosclerosis. Nat Med, 1, 74-9.
93. Ivanovic, V., Melman, A., Davis-Joseph, B., Valcic, M. and Geliebter, J. (1995) Elevated plasma levels of TGF-beta 1 in patients with invasive prostate cancer. Nat Med, 1, 282-4.
94. Kulkarni, A.B., Ward, J.M., Yaswen, L., Mackall, C.L., Bauer, S.R., Huh, C.G., Gress, R.E. and Karlsson, S. (1995) Transforming growth factor-beta 1 null mice. An animal model for inflammatory disorders. Am J Pathol, 146, 264-75.
95. Syrris, P., Carter, N.D., Metcalfe, J.C., Kemp, P.R., Grainger, D.J., Kaski, J.C., Crossman, D.C., Francis, S.E., Gunn, J., Jeffery, S. and Heathcote, K. (1998) Transforming growth factor-beta1 gene polymorphisms and coronary artery disease. Clin Sci (Lond), 95, 659-67.
96. Pardo, R., Malaga, S., Coto, E., Navarro, M., Alvarez, V., Espinosa, L., Alvarez, R., Vallo, A., Loris, C. and Braga, S. (2003) Renin-angiotensin system polymorphisms and renal scarring. Pediatr Nephrol, 18, 110-4.
97. Yoneda, A., Oue, T. and Puri, P. (2001) Angiotensin-converting enzyme genotype distribution in familial vesicoureteral reflux. Pediatr Surg Int, 17, 308-11.
98. Haszon, I., Friedman, A.L., Papp, F., Bereczki, C., Baji, S., Bodrogi, T., Karoly, E., Endreffy, E. and Turi, S. (2002) ACE gene polymorphism and renal scarring in primary vesicoureteric reflux. Pediatr Nephrol, 17, 1027-31.
99. Ohtomo, Y., Nagaoka, R., Kaneko, K., Fukuda, Y., Miyano, T. and Yamashiro, Y. (2001) Angiotensin converting enzyme gene polymorphism in primary vesicoureteral reflux. Pediatr Nephrol, 16, 648-52.
100. Park, H.W., Koo, J.W., Kim, J.S., Ha, I.S., Cheong, H.I. and Choi, Y. (2000) Association of angiotensin I converting enzyme gene polymorphism with reflux nephropathy in children. Nephron, 86, 52-5.
101. Yeh, F. and Boyle, T. (1996) Popgene version 1.1: microsoft window-based software for population genetics analysis.
102. Hill, W.G. (1974) Estimation of linkage disequilibrium in randomly mating populations. Heredity, 33, 229-39.
103. 林文郎,中華民國九十二年三月十五日,ACE及AT1R基因啟動子多型性的功能性分析,行政院國家科學委員會補助大專學生參與專題研究計畫研究成果報告。
104. Paul, H., Galton, D. and Stocks, J. (1987) DNA polymorphic patterns and haplotype arrangements of the apo A-1, apo C-III, apo A-IV gene cluster in different ethnic groups. Hum Genet, 75, 264-8.
105. Leitersdorf, E., Chakravarti, A. and Hobbs, H.H. (1989) Polymorphic DNA haplotypes at the LDL receptor locus. Am J Hum Genet, 44, 409-21.
106. Thompson, E.A., Deeb, S., Walker, D. and Motulsky, A.G. (1988) The detection of linkage disequilibrium between closely linked markers: RFLPs at the AI-CIII apolipoprotein genes. Am J Hum Genet, 42, 113-24.
107. Arkwright, P.D., Laurie, S., Super, M., Pravica, V., Schwarz, M.J., Webb, A.K. and Hutchinson, I.V. (2000) TGF-beta(1) genotype and accelerated decline in lung function of patients with cystic fibrosis. Thorax, 55, 459-62.
108. Gomez, R.A. and Norwood, V.F. (1995) Developmental consequences of the renin-angiotensin system. Am J Kidney Dis, 26, 409-31.
109. Gomez, R.A. (1998) Role of angiotensin in renal vascular development. Kidney Int Suppl, 67, S12-6.
110. Jung, F.F., Bouyounes, B., Barrio, R., Tang, S.S., Diamant, D. and Ingelfinger, J.R. (1993) Angiotensin converting enzyme in renal ontogeny: hypothesis for multiple roles. Pediatr Nephrol, 7, 834-40.
111. Tufro-McReddie, A., Harrison, J.K., Everett, A.D. and Gomez, R.A. (1993) Ontogeny of type 1 angiotensin II receptor gene expression in the rat. J Clin Invest, 91, 530-7.
112. Kakuchi, J., Ichiki, T., Kiyama, S., Hogan, B.L., Fogo, A., Inagami, T. and Ichikawa, I. (1995) Developmental expression of renal angiotensin II receptor genes in the mouse. Kidney Int, 47, 140-7.
113. Esther, C.R., Jr., Howard, T.E., Marino, E.M., Goddard, J.M., Capecchi, M.R. and Bernstein, K.E. (1996) Mice lacking angiotensin-converting enzyme have low blood pressure, renal pathology, and reduced male fertility. Lab Invest, 74, 953-65.
114. Barr, M., Jr. (1994) Teratogen update: angiotensin-converting enzyme inhibitors. Teratology, 50, 399-409.
115. Hohenfellner, K., Fogo, A. and Kon, V. (1999) Renin-angiotensin genes in renal development and the occurrence and progression of renal diseases. Semin Nephrol, 19, 148-54.
116. Woolf, A.S. (2000) A molecular and genetic view of human renal and urinary tract malformations. Kidney Int, 58, 500-12.
117. Bernstein, K.E. (1998) ACE knockout mice--lessons for adult nephrology. Nephrol Dial Transplant, 13, 2991-4.
118. Choi, M.E., Liu, A. and Ballermann, B.J. (1997) Differential expression of transforming growth factor-beta receptors in rat kidney development. Am J Physiol, 273, F386-95.
119. Rogers, S.A., Ryan, G., Purchio, A.F. and Hammerman, M.R. (1993) Metanephric transforming growth factor-beta 1 regulates nephrogenesis in vitro. Am J Physiol, 264, F996-1002.
120. Yang, S.P., Woolf, A.S., Yuan, H.T., Scott, R.J., Risdon, R.A., O'Hare, M.J. and Winyard, P.J. (2000) Potential biological role of transforming growth factor-beta1 in human congenital kidney malformations. Am J Pathol, 157, 1633-47.
121. Chevalier, R.L. (1999) Molecular and cellular pathophysiology of obstructive nephropathy. Pediatr Nephrol, 13, 612-9.
122. Ichikawa, I. (1996) Will angiotensin II receptor antagonists be renoprotective in humans? Kidney Int, 50, 684-92.
123. Lama, G., Salsano, M.E., Pedulla, M., Grassia, C. and Ruocco, G. (1997) Angiotensin converting enzyme inhibitors and reflux nephropathy: 2-year follow-up. Pediatr Nephrol, 11, 714-8.
124. Kagami, S., Border, W.A., Miller, D.E. and Noble, N.A. (1994) Angiotensin II stimulates extracellular matrix protein synthesis through induction of transforming growth factor-beta expression in rat glomerular mesangial cells. J Clin Invest, 93, 2431-7.
125. Ozen, S., Alikasifoglu, M., Saatci, U., Bakkaloglu, A., Besbas, N., Kara, N., Kocak, H., Erbas, B., Unsal, I. and Tuncbilek, E. (1999) Implications of certain genetic polymorphisms in scarring in vesicoureteric reflux: importance of ACE polymorphism. Am J Kidney Dis, 34, 140-5.
126. Tsai, C.T., Fallin, D., Chiang, F.T., Hwang, J.J., Lai, L.P., Hsu, K.L., Tseng, C.D., Liau, C.S. and Tseng, Y.Z. (2003) Angiotensinogen gene haplotype and hypertension: interaction with ACE gene I allele. Hypertension, 41, 9-15.
127. Morris, B.J., Zee, R.Y., Ying, L.H. and Griffiths, L.R. (1993) Independent, marked associations of alleles of the insulin receptor and dipeptidyl carboxypeptidase-I genes with essential hypertension. Clin Sci (Lond), 85, 189-95.
128. Rosatto, N., Pontremoli, R., De Ferrari, G. and Ravazzolo, R. (1999) Intron 16 insertion of the angiotensin converting enzyme gene and transcriptional regulation. Nephrol Dial Transplant, 14, 868-71.
129. Yanai, K., Nibu, Y., Murakami, K. and Fukamizu, A. (1996) A cis-acting DNA element located between TATA box and transcription initiation site is critical in response to regulatory sequences in human angiotensinogen gene. J Biol Chem, 271, 15981-6.
130. Plumb, M., Frampton, J., Wainwright, H., Walker, M., Macleod, K., Goodwin, G. and Harrison, P. (1989) GATAAG; a cis-control region binding an erythroid-specific nuclear factor with a role in globin and non-globin gene expression. Nucleic Acids Res, 17, 73-92.