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First confirmation of genetic association with MMP9 and exudative age-related macular degeneration (AMD).

A novel research report, published in Ophthalmology Science (Jan. 11th 2021) has identified a genetic association between the MMP9 gene (matrix metalloproteinase-9) and exudative AMD.  According to the researchers, the study provides the first independent confirmation for the MMP9 locus, “further implicating a role for extracellular matrix abnormalities in choroidal neovascularization”.  The study of 1,712 subjects with AMD (672 non-exudative, 1,040 exudative) of predominantly northern European descent has identified at least three SNPs (single nucleotide polymorphisms), likely to follow up in due course to define the specific molecular pathologies.


It is well known that a range of causes of AMD has a combination of both genetic risk factors and environmental cues, including smoking, diet and other influences.  In terms of genetics, there are >30 genetic risk factors, such as complement factor H, complement 2 and 3, complement factor B and other aspects of extracellular matrix biology that can cause AMD.  Interestingly, while many of these risk factors can be reported for developing AMD of any type, matrix metalloproteinase-9 (MMP9) is the only gene that has been associated specifically with the development of exudative AMD.  In the current study, researchers have now identified three SNPs in the MMP9 locus (rs4810482, rs17576, and rs17577), highly associated with exudative AMD in patient population recruited by an International AMD Genetics Consortium (IAMDGC). The MMP9 SNPs reported rs4810482, with an odds ratio of 0.83, p=0.010; rs17576, with an odds ratio of 0.86, p=0.046; and finally, rs17577, with an odds ratio of 0.81, p=0.041). In assessing the analysis of the outcomes, the researchers have supported several plausible biological reasons for MMP9, not least of all, the use of the protease being involved in the remodelling of the extracellular matrix and interactions with collagens I and IV, elastin and fibrinogen – a significant smoking gun. In addition, the activity of MMP9 increasing in Bruch’s membrane, and associated with age, also identify an association with TIMP3 shows several other clinical characteristics.


While the MMP9 loci were re-analysed in detail. of the three SNPs, (rs4810482, rs17576, and rs17577), one locus, rs17576, had the strongest statistical association with exudative AMD (p = 3.8×10-9).  This SNP had encoded an A-to-G change that alters the 279th amino acid in MMP9 from glutamine to arginine (Q279R). The result of the study now shows that there may be a treasure trove of data coming in the months and years ahead and these analyses may soon be able to provide genetic and pharmacological opportunities leading to drug-able targets in due course.