Polymorphisms in the Human Matrix Metalloproteinase Genes MMP1, MMP3, and MMP9: Genetic Risk Factors of Primary Open Angle Glaucoma?

Matrix metalloproteinases (MMPs) fulfill diverse important molecular functions and play pivotal roles in development, tissue morphogenesis, repair, aging, and inflammatory processes. MMPs are also important disease modulating factors, such as cancer, cardiovascular disease, rheumatoid arthritis or macular degeneration. Functional genetic variants have been described to fine-tune MMP activities at the gene transcriptional level and have been associated with increased genetic risk of e.g. arteriosclerosis or cancer. MMPs are also assumed to play a major role in the remodeling of the extracellular matrix (ECM) in the optic nerve head during glaucomatous optic neuropathy. MMP-1, MMP-3 and MMP-9 have been shown to be up-regulated in a variety of animal models of glaucoma. Here, we study three promoter SNPs within the genes encoding three members of the MMP family. By assessing the prevalence of genetic variants associated with either increased/decreased enzyme activity, we will (i) estimate their contribution to the genetic risk of developing primary open angle glaucoma (POAG) and (ii) investigate the potential role of MMPs in the functional pathology of POAG.