The Association between TGF-β1 G915C (Arg25Pro) Polymorphism and the Development of Primary Open Angle Glaucoma: A Case-Control Study



The purpose of the current study was to identify the potential association between Single Nucleotide Polymorphism (SNP) TGFβ1 +915 (C or G) in codon 25 and Primary Open Angle Glaucoma (POAG).

Overall, 88 cases with POAG and a control group of 52 healthy individuals were recruited from the First Ophthalmology Department of Athens University. DNA was isolated from whole blood samples and genotype frequencies for the polymorphism rs1800471 (G915C, Arg25Pro) of the TGF-β1 gene were assessed.

Genotype distribution frequencies for the polymorphism rs1800471 (G915C, Arg25Pro) of the TGF-β1 gene were not statistically different between patients with POAG and control subjects.

The present study failed to determine any significant genotypic association with POAG, despite the fact that the presence of the C allele was scarcely increased in the POAG when compared with the control group.


Roberts AB, Sporn MB, Assoian RK, Smith JM, Roche NS, Wakefield LM, et al. Transforming growth factor type beta: rapid induction of fibrosis and angiogenesis in vivo and stimulation of collagen formation in vitro. Proc Natl Acad Sci U S A. 1986;83(12):4167-71. pmid: 2424019

Border WA, Noble NA. Transforming growth factor beta in tissue fibrosis. N Engl J Med. 1994;331(19):1286-92. doi: 10.1056/NEJM199411103 311907 pmid: 7935686

O'Kane S, Ferguson MW. Transforming growth factor beta s and wound healing. Int J Biochem Cell Biol. 1997;29(1):63-78. pmid: 9076942

Cousins SW, McCabe MM, Danielpour D, Streilein JW. Identification of transforming growth factor-beta as an immunosuppressive factor in aqueous humor. Invest Ophthalmol Vis Sci. 1991;32(8):2201-11. pmid: 2071334

Jampel HD, Roche N, Stark WJ, Roberts AB. Transforming growth factor-beta in human aqueous humor. Curr Eye Res. 1990;9(10):963-9. pmid: 2276273

Tripathi RC, Li J, Chan WF, Tripathi BJ. Aqueous humor in glaucomatous eyes contains an increased level of TGF-beta 2. Exp Eye Res. 1994;59(6):723-7. pmid: 7698265

Ochiai Y, Ochiai H. Higher concentration of transforming growth factor-beta in aqueous humor of glaucomatous eyes and diabetic eyes. Jpn J Ophthalmol. 2002;46(3):249-53. pmid: 12063033

Ozcan AA, Ozdemir N, Canataroglu A. The aqueous levels of TGF-beta2 in patients with glaucoma. Int Ophthalmol. 2004;25(1):19-22. pmid: 15085971

Min SH, Lee TI, Chung YS, Kim HK. Transforming growth factor-beta levels in human aqueous humor of glaucomatous, diabetic and uveitic eyes. Korean J Ophthalmol. 2006;20(3):162-5. doi: 10.3341/kjo.2006 .20.3.162 pmid: 17004630

Stefan C, Dragomir L, Dumitrica DM, Ursaciuc C, Dobre M, Surcel M. [TGF-beta2 involvements in open angle glaucoma]. Oftalmologia. 2008;52(3):110-2. pmid: 19149129

Inatani M, Tanihara H, Katsuta H, Honjo M, Kido N, Honda Y. Transforming growth factor-beta 2 levels in aqueous humor of glaucomatous eyes. Graefes Arch Clin Exp Ophthalmol. 2001;239(2):109-13. pmid: 11372538

Yoneda K, Nakano M, Mori K, Kinoshita S, Tashiro K. Disease-related quantitation of TGF-beta3 in human aqueous humor. Growth Factors. 2007;25(3):160-7. doi: 10.1080/08977190701723505 pmid: 18049952

Yu XB, Sun XH, Dahan E, Guo WY, Qian SH, Meng FR, et al. Increased levels of transforming growth factor-betal and -beta2 in the aqueous humor of patients with neovascular glaucoma. Ophthalmic Surg Lasers Imaging. 2007;38(1):6-14. pmid: 17278530

Yamamoto N, Itonaga K, Marunouchi T, Majima K. Concentration of transforming growth factor beta2 in aqueous humor. Ophthalmic Res. 2005;37(1):29-33. doi: 10.1159/000083019 pmid: 15637419

Picht G, Welge-Luessen U, Grehn F, Lutjen-Drecoll E. Transforming growth factor beta 2 levels in the aqueous humor in different types of glaucoma and the relation to filtering bleb development. Graefes Arch Clin Exp Ophthalmol. 2001;239(3):199-207. pmid: 11405069

Trivedi RH, Nutaitis M, Vroman D, Crosson CE. Influence of race and age on aqueous humor levels of transforming growth factor-beta 2 in glaucomatous and nonglaucomatous eyes. J Ocul Pharmacol Ther. 2011;27(5):477-80. doi: 10.1089/jop.2010.0100 pmid: 21034224

Wordinger RJ, Clark AF, Agarwal R, Lambert W, McNatt L, Wilson SE, et al. Cultured human trabecular meshwork cells express functional growth factor receptors. Invest Ophthalmol Vis Sci. 1998;39(9):1575-89. pmid: 9699547

Borisuth NS, Tripathi BJ, Tripathi RC. Identification and partial characterization of TGF-beta 1 receptors on trabecular cells. Invest Ophthalmol Vis Sci. 1992;33(3):596-603. pmid: 1312071

Tripathi RC, Li J, Borisuth NS, Tripathi BJ. Trabecular cells of the eye express messenger RNA for transforming growth factor-beta 1 and secrete this cytokine. Invest Ophthalmol Vis Sci. 1993;34(8):2562-9. pmid: 7686895

Khaw PT, Occleston NL, Schultz G, Grierson I, Sherwood MB, Larkin G. Activation and suppression of fibroblast function. Eye (Lond). 1994;8 ( Pt 2):188-95. doi: 10.1038/eye.1994.44 pmid: 7958020

Khaw PT, Chang L, Wong TT, Mead A, Daniels JT, Cordeiro MF. Modulation of wound healing after glaucoma surgery. Curr Opin Ophthalmol. 2001;12(2):143-8. pmid: 11224722

De La Paz MA, Epstein DL. Effect of age on superoxide dismutase activity of human trabecular meshwork. Invest Ophthalmol Vis Sci. 1996;37(9):1849-53. pmid: 8759353

Koliakos GG, Schlotzer-Schrehardt U, Konstas AG, Bufidis T, Georgiadis N, Dimitriadou A. Transforming and insulin-like growth factors in the aqueous humour of patients with exfoliation syndrome. Graefes Arch Clin Exp Ophthalmol. 2001;239(7):482-7. pmid: 11521691

Tamm ER, Siegner A, Baur A, Lutjen-Drecoll E. Transforming growth factor-beta 1 induces alpha-smooth muscle-actin expression in cultured human and monkey trabecular meshwork. Exp Eye Res. 1996;62(4):389-97. doi: 10.1006/exer.1996.0044 pmid: 8795457

Vittitow J, Borras T. Genes expressed in the human trabecular meshwork during pressure-induced homeostatic response. J Cell Physiol. 2004;201(1):126-37. doi: 10.1002/jcp.20030 pmid: 15281095

Li J, Tripathi BJ, Tripathi RC. Modulation of pre-mRNA splicing and protein production of fibronectin by TGF-beta2 in porcine trabecular cells. Invest Ophthalmol Vis Sci. 2000;41(11):3437-43. pmid: 11006236

Zhao X, Ramsey KE, Stephan DA, Russell P. Gene and protein expression changes in human trabecular meshwork cells treated with transforming growth factor-beta. Invest Ophthalmol Vis Sci. 2004;45(11):4023-34. doi: 10.1167/iovs.04-0535 pmid: 15505052

Nakamura Y, Hirano S, Suzuki K, Seki K, Sagara T, Nishida T. Signaling mechanism of TGF-beta1-induced collagen contraction mediated by bovine trabecular meshwork cells. Invest Ophthalmol Vis Sci. 2002;43(11):3465-72. pmid: 12407157

Nakamura Y, Sagara T, Seki K, Hirano S, Nishida T. Permissive effect of fibronectin on collagen gel contraction mediated by bovine trabecular meshwork cells. Invest Ophthalmol Vis Sci. 2003;44(10):4331-6. pmid: 14507877

Das P, Golde T. Dysfunction of TGF-beta signaling in Alzheimer's disease. J Clin Invest. 2006;116(11):2855-7. doi: 10.1172/JCI30284 pmid: 17080189

Mehta JL, Attramadal H. The TGFbeta superfamily in cardiovascular biology. Cardiovasc Res. 2007;74(2):181-3. doi: 10.1016/j.cardiores.2007.03.01 1 pmid: 17389143

Agarwal R, Agarwal P. Future target molecules in antiglaucoma therapy: tgf-Beta may have a role to play. Ophthalmic Res. 2010;43(1):1-10. doi: 10.1159 /000246571 pmid: 19829006

Cambien F, Ricard S, Troesch A, Mallet C, Generenaz L, Evans A, et al. 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. 1996;28(5):881-7. pmid: 8901839

Grainger DJ, Heathcote K, Chiano M, Snieder H, Kemp PR, Metcalfe JC, et al. Genetic control of the circulating concentration of transforming growth factor type beta1. Hum Mol Genet. 1999;8(1):93-7. pmid: 9887336

Sripriya S, George R, Arvind H, Baskaran M, Raju P, Ramesh SV, et al. Transforming growth factor beta-1 -509C>T polymorphism in Indian patients with primary open angle glaucoma. Mol Diagn Ther. 2007;11(3):151-4. pmid: 17570736

Sandhya A, Bindu C, Reddy K, Vishnupriya S. TGFB1 codon 10 polymorphism and its association with the development of myopia: a case-control study. Biol Med. 2011;3(4):18-24.

Atabay B, Oren H, Irken G, Kizildag S, Tunali S, Turker M, et al. Role of transforming growth factor-beta 1 gene polymorphisms in childhood idiopathic thrombocytopenic purpura. J Pediatr Hematol Oncol. 2003;25(11):885-9. pmid: 14608199

Tag CG, Mengsteab S, Hellerbrand C, Lammert F, Gressner AM, Weiskirchen R. Analysis of the transforming growth factor-beta1 (TGF-beta1) codon 25 gene polymorphism by LightCycler-analysis in patients with chronic hepatitis C infection. Cytokine. 2003;24(5):173-81. pmid: 14596813

Chudgar SM, Deng P, Maddala R, Epstein DL, Rao PV. Regulation of connective tissue growth factor expression in the aqueous humor outflow pathway. Mol Vis. 2006;12:1117-26. pmid: 17093396

Zhong L, Li M. [Transforming growth factor-beta1 induced cultured human trabecular cells to produce elastin]. Zhonghua Yan Ke Za Zhi. 1999;35(5):383-5. pmid: 11835846

Read AT, Chan DW, Ethier CR. Actin structure in the outflow tract of normal and glaucomatous eyes. Exp Eye Res. 2007;84(1):214-26. pmid: 17219625

Clark AF, Wilson K, McCartney MD, Miggans ST, Kunkle M, Howe W. Glucocorticoid-induced formation of cross-linked actin networks in cultured human trabecular meshwork cells. Invest Ophthalmol Vis Sci. 1994;35(1):281-94. pmid: 8300356

Tan JC, Peters DM, Kaufman PL. Recent developments in understanding the pathophysiology of elevated intraocular pressure. Curr Opin Ophthalmol. 2006;17(2):168-74. doi: 10.1097/ .55240.18 pmid: 16552252

Liton PB, Liu X, Challa P, Epstein DL, Gonzalez P. Induction of TGF-beta1 in the trabecular meshwork under cyclic mechanical stress. J Cell Physiol. 2005;205(3):364-71. doi: 10.1002/jcp.20404 pmid: 15895394

Flugel-Koch C, Ohlmann A, Fuchshofer R, Welge-Lussen U, Tamm ER. Thrombospondin-1 in the trabecular meshwork: localization in normal and glaucomatous eyes, and induction by TGF-beta1 and dexamethasone in vitro. Exp Eye Res. 2004;79(5):649-63. doi: 10.1016/j.exer.2004.07.005 pmid: 15500824

Tamm ER, Russell P, Epstein DL, Johnson DH, Piatigorsky J. Modulation of myocilin/TIGR expression in human trabecular meshwork. Invest Ophthalmol Vis Sci. 1999;40(11):2577-82. pmid: 10509652

Liton PB, Li G, Luna C, Gonzalez P, Epstein DL. Cross-talk between TGF-beta1 and IL-6 in human trabecular meshwork cells. Mol Vis. 2009;15:326-34. pmid: 19209241

Fukuchi T, Ueda J, Hanyu T, Abe H, Sawaguchi S. Distribution and expression of transforming growth factor-beta and platelet-derived growth factor in the normal and glaucomatous monkey optic nerve heads. Jpn J Ophthalmol. 2001;45(6):592-9. pmid: 11754900

Kirwan RP, Crean JK, Fenerty CH, Clark AF, O'Brien CJ. Effect of cyclical mechanical stretch and exogenous transforming growth factor-beta1 on matrix metalloproteinase-2 activity in lamina cribrosa cells from the human optic nerve head. J Glaucoma. 2004;13(4):327-34. pmid: 15226662

Awad MR, El-Gamel A, Hasleton P, Turner DM, Sinnott PJ, Hutchinson IV. 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. 1998;66(8):1014-20. pmid: 9808485

Challa P. Glaucoma genetics. Int Ophthalmol Clin. 2008;48(4):73-94. doi: 10.1097/IIO.0b013e318187e7 1a pmid: 18936638

Challa P. Genetics of adult glaucoma. Int Ophthalmol Clin. 2011;51(3):37-51. doi: 10.1097/IIO.0b013e318 21e52fe pmid: 21633237

Robertson JV, Golesic E, Gauldie J, West-Mays JA. Ocular gene transfer of active TGF-beta induces changes in anterior segment morphology and elevated IOP in rats. Invest Ophthalmol Vis Sci. 2010;51(1):308-18. doi: 10.1167/iovs.09-3380 pmid: 19696167

Prendes MA, Harris A, Wirostko BM, Gerber AL, Siesky B. The role of transforming growth factor beta in glaucoma and the therapeutic implications. Br J Ophthalmol. 2013;97(6):680-6. doi: 10.1136/bjophth almol-2011-301132 pmid: 23322881

Full Text: Full Text PDF

Creative Commons License
This work is licensed under a Creative Commons Attribution 3.0 License.