Lack of Association between the C677T Single Nucleotide Polymorphism of the MTHFR Gene and Glaucoma in Iranian Patients
-
Navid Nilforoushan
,
Sevil Aghapour
,
Reza Raoofian
,
Samira Saee Rad
,
Wayne K. Greene
,
Ghasem Fakhraie
,
Mansour Heidari
Abstract
Glaucoma is a major cause of blindness worldwide. A single nucleotide polymorphism of the MTHFR gene (C677T) has been associated with susceptibility to this disease, although this is controversial in the last decade. In this study, the possible association between the MTHFR C677T polymorphism and the risk of developing primary open angle (POAG) and pseudoexfoliation glaucoma (PEXG) was investigated. For this, a prospective study consisting of 73 POAG, 85 PEXG and 90 matched controls was undertaken in an Iranian population. Genomic DNA was extracted from whole blood. Genotyping of all individuals for the MTHFR C677T polymorphism was conducted using the PCR-RFLP technique. Our findings revealed no significant association between the MTHFR C677T polymorphism in POAG and PEXG compared with controls. Consistent with several other studies, our analysis suggests that the MTHFR C677T polymorphism is unlikely to be a factor contributing to the risk of developing specific forms of glaucoma.
Quigley HA. Number of people with glaucoma worldwide. Br J Ophthalmol 1996;80(5):389-93.
Quigley HA, Broman AT. The number of people with glaucoma worldwide in 2010 and 2020. Br J Ophthalmol 2006;90(3):262-7.
Osborne NN, Wood JP, Chidlow G, Bae JH, Melena J, Nash MS. Ganglion cell death in glaucoma: what do we really know? Br J Ophthalmol 1999;83(8):980-6.
Quigley HA, Green WR. The histology of human glaucoma cupping and optic nerve damage: clinicopathologic correlation in 21 eyes. Ophthalmology 1979;86(10):1803-30.
Lipton SA, Kim WK, Choi YB, Kumar S, D'Emilia DM, Rayudu PV, Arnelle DR, Stamler JS.. Neurotoxicity associated with dual actions of homocysteine at the Nmethyl- D-aspartate receptor. Proc Natl Acad Sci U S A 1997;94(11):5923-8.
Miner SE, Evrovski J, Cole DE. Clinical chemistry and molecular biology of homocysteine metabolism: an update. Clin Biochem 1997;30(3):189-201.
Christensen B, Frosst P, Lussier-Cacan S, Selhub J, Goyette P, Rosenblatt DS, Genest J Jr, Rozen R. Correlation of a common mutation in the methylenetetrahydrofolate reductase gene with plasma homocysteine in patients with premature coronary artery disease. Arterioscler Thromb Vasc Biol 1997;17(3):569-73.
Ma J, Stampfer MJ, Hennekens CH, Frosst P, Selhub J, Horsford J, Malinow MR, Willett WC, Rozen R. Methylenetetrahydrofolate reductase polymorphism, plasma folate, homocysteine, and risk of myocardial infarction in US physicians. Circulation 1996;94(10):2410-6.
Franco RF, Araujo AG, Guerreiro JF, Elion J, Zago MA. Analysis of the 677 C-->T mutation of the methylenetetrahydrofolate reductase gene in different ethnic groups. Thromb Haemost 1998;79(1):119-21.
Pepe G, Camacho Vanegas O, Giusti B, Brunelli T, Marcucci R, Attanasio M, Rickards O, De Stefano GF, Prisco D, Gensini GF, Abbate R. Heterogeneity in world distribution of the thermolabile C677T mutation in 5,10- methylenetetrahydrofolate reductase. Am J Hum Genet 1998;63(3):917-20.
Moore P, El-sherbeny A, Roon P, Schoenlein PV, Ganapathy V, Smith SB. Apoptotic cell death in the mouse retinal ganglion cell layer is induced in vivo by the excitatory amino acid homocysteine. Exp Eye Res 2001;73(1):45-57.
Leibovitch I, Kurtz S, Shemesh G, Goldstein M, Sela BA, Lazar M, Loewenstein A. Hyperhomocystinemia in pseudoexfoliation glaucoma. J Glaucoma 2003;12(1):36-9.
Schlötzer-Schrehardt U, Lommatzsch J, Küchle M, Konstas AG, Naumann GO. Matrix metalloproteinases and their inhibitors in aqueous humor of patients with pseudoexfoliation syndrome/glaucoma and primary openangle glaucoma. Invest Ophthalmol Vis Sci 2003;44(3):1117-25.
Chango A, Potier De Courcy G, Boisson F, Guilland JC, Barbé F, Perrin MO, Christidès JP, Rabhi K, Pfister M, Galan P, Hercberg S, Nicolas JP. 5,10-methylenetetrahydrofolate reductase common mutations, folate status and plasma homocysteine in healthy French adults of the Supplementation en Vitamines et Mineraux Antioxydants (SU.VI.MAX) cohort. Br J Nutr 2000;84(6):891-6.
Goyette P, Frosst P, Rosenblatt DS, Rozen R. Seven novel mutations in the methylenetetrahydrofolate reductase gene and genotype/phenotype correlations in severe methylenetetrahydrofolate reductase deficiency. Am J Hum Genet 1995;56(5):1052-9.
Jünemann AG, von Ahsen N, Reulbach U, Roedl J, Bönsch D, Kornhuber J, Kruse FE, Bleich S. C677T variant in the methylentetrahydrofolate reductase gene is a genetic risk factor for primary open-angle glaucoma. Am J Ophthalmol 2005;139(4):721-3.
Turacli ME, Tekeli O, Ozdemir F, Akar N. Methylenetetrahydrofolate reductase 677 C-T and homocysteine levels in Turkish patients with pseudoexfoliation. Clin Experiment Ophthalmol 2005;33(5):505-8.
Fingert JH, Kwon YH, Moore PA, Johnston RM, Kim KY, Sheffield VC, Alward WL, Stone EM. The C677T variant in the methylenetetrahydrofolate reductase gene is not associated with disease in cohorts of pseudoexfoliation glaucoma and primary open-angle glaucoma patients from Iowa. Ophthalmic Genet 2006;27(2):39-41.
Mossbock G, Weger M, Faschinger C, Steinbrugger I, Temmel W, Schmut O, Renner W, Hufnagel C, Stanger O. Methylenetetrahydrofolatereductase (MTHFR) 677C>T polymorphism and open angle glaucoma. Mol Vis 2006;12:356-9.
Mabuchi F, Tang S, Kashiwagi K, Yamagata Z, Iijima H, Tsukahara S. Methylenetetrahydrofolate reductase gene polymorphisms c.677C/T and c.1298A/C are notassociated with open angle glaucoma Mol Vis 2006;12:735-9.
Clement CI, Goldberg I, Healey PR, Graham SL. Plasma homocysteine, MTHFR gene mutation, and open-angle glaucoma. J Glaucoma 2009;18(1):73-8.
Fan BJ, Chen T, Grosskreutz C, Pasquale L, Rhee D, DelBono E, Haines JL, Wiggs JL. Lack of association ofpolymorphisms in homocysteine metabolism genes with pseudoexfoliation syndrome and glaucoma. Mol Vis 2008;14:2484-91.
Micheal S, Qamar R, Akhtar F, Khan MI, Khan WA,Ahmed A. MTHFR gene C677T and A1298C polymorphisms and homocysteine levels in primary open angle and primary closed angle glaucoma. Mol Vis 2009;15:2268-78.
Ferechide D, Radulescu D. Hyperhomocysteinemia in renal diseases. J Med Life 2009;2(1):53-9.
La Regina M, Orlandini F, Prisco D, Dentali F.Homocysteine in vascular behcet disease: a meta-analysis. Arterioscler Thromb Vasc Biol 2010;30(10):2067-74.
Sottilotta G, Oriana V, Latella C, Luise F, Piromalli A, Ramirez F, Mammi C, Occhiuto A, Lombardo VT. Role of hyperhomocystinemia in retinal vascular occlusive disease. Clin Appl Thromb Hemost 2007;13(1):104-7.
Sottilotta G, Siboni SM, Latella C, Oriana V, Romeo E, Santoro R, Consonni D, Trapani Lombardo V.mHyperhomocysteinemia and C677T MTHFR genotype in patients with retinal vein thrombosis. Clin Appl Thromb Hemost 2010;16(5):549-53.
Blacher J, Montalescot G, Ankri A, Chadefaux-Vekemans B, Benzidia R, Grosgogeat Y, Kamoun P, Thomas D. Hyperhomocysteinemia in coronary artery diseases. Apropos of a study on 102 patients. Arch Mal Coeur Vaiss 1996;89(10):1241-6.
Marszall ML, Makarowski R, Hinc S, Klos M, Czarnowski W. Hiperhomocysteinemia in active and passive smokers and the levels of folate and vitamin B6 in plasma. PrzeglLek 2008;65(10):486-90.
Summers CM, Mitchell LE, Stanislawska-Sachadyn A, Baido SF, Blair IA, Von Feldt JM, Whitehead AS. Genetic and lifestyle variables associated with homocysteine concentrations and the distribution of folate derivatives in healthy premenopausal women. Birth Defects Res A Clin Mol Teratol 2010;88(8):679-88.
| Files | ||
| Issue | Vol 50, No 3 (2012) | |
| Section | Original Article(s) | |
| Keywords | ||
| Primary open angle glaucoma Pseudoexfoliation glaucoma MTHFR PCR-RFLP | ||
| Rights and permissions | |
|
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
