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J. Blasiak, K. Janik-Papis, A. Rewerska, M. Zaras, J. P. Szaflik, J. Szaflik; An Association Between the -1296C>T Polymorphism of the Tissue Inhibitor of Matrix Metalloproteinase-3 Gene and Age Related Macular Degeneration. Invest. Ophthalmol. Vis. Sci. 2010;51(13):1275.
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Mutations in the tissue inhibitor of matrix metalloproteinase-3 (Timp-3) gene cause Sorsby fundus dystrophy, a hereditary macular degenerative disease characterized by extracellular matrix (ECM) irregularities in Bruch's membrane. This disease has a strong similarity to age related macular degeneration (AMD). Moreover, eyes with AMD demonstrate accumulation of specific deposits and ECM molecules under the retinal pigment epithelium and metalloproteinases are crucial regulators of basement membrane and ECM turnover. That is why we investigated polymorphisms in the promoter region of the Timp-3 gene, which may primarily affect the level of transcription, in wet and dry forms of AMD.
We studied a C>T transition at -1296 in the Timp-3 gene (the -1296C>T polymorphism, rs9619331) in peripheral blood lymphocytes of 175 patients with wet AMD, 100 patients with dry AMD and 101 controls. Genotypes of the -1296C>T polymorphism were determined by the PCR-RFLP.
We observed an association between the CT genotype of the -1296C>T polymorphism of the Timp-3 gene and the occurrence of the wet form of AMD (OR 2.16, 95% Cl 1.05-4.48). On the other hand, the CC genotype protected against the wet form of AMD (OR 0.36, 95% Cl 0.14-0.93). We did not find any association between the occurrence of dry form of AMD and this polymorphism.
The -1296 polymorphism of the Timp-3 gene may influence the level of its expression and in this way the thickness of Bruch's membrane, which may be crucial for AMD pathogenesis. Therefore, the variability of the Timp-3 gene may modulate the susceptibility to AMD.This work was supported by the grant N N402 248336 from the Ministry of Science and Higher Education.
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