A study now validates a long-suspected connection between the matrix metalloproteinase-9 (MMP-9) gene on chromosome 20 and the development of exudative age-related macular degeneration (wet AMD), according to findings published in Ophthalmology Science.
Prior research had found that single nucleotide polymorphisms near the MMP-9 gene are associated with AMD, according to the study. Some studies also have suggested that variants at the MMP-9 locus are associated with exudative AMD. While many risk factors for developing AMD of any type have been identified, only 1 gene — MMP-9 — has been linked specifically with the exudative type.
To further evaluate this association and to identify additional associated single nucleotide polymorphisms, investigators re-analyzed data from patients in Iowa from the International AMD Genetics Consortium (IAMDGC). In total, 1712 subjects from Iowa with AMD (672 non-exudative, 1040 exudative) of predominantly northern European descent were included in the analysis.
The cohort was genotyped with 3 single nucleotide polymorphisms. Firth regression was used to evaluate the association between MMP-9 single nucleotide polymorphism genotypes and exudative AMD. Additionally, researchers developed a polymerase chain reaction-based assay to genotype the cohort at a short tandem repeat polymorphism (STRP) at the MMP-9 locus.
The Iowa-based team found that 3 single nucleotide polymorphisms in the MMP-9 locus were heavily associated with exudative AMD in patient cohorts of the IAMDGC. These single nucleotide polymorphisms also were associated with exudative AMD in the Iowa cohort (rs4810482, odds ratio 0.83, P =.010; rs17576, odds ratio 0.86, P =.046; and rs17577, odds ratio 0.81, P =.041). Genotyping the Iowa cohort detected a 4bp STRP — (TTTC)n — at the rs142450006 locus that is highly polymorphic and significantly associated with exudative AMD (odds ratio 0.77, P=0.016), according to researchers.
Researchers note several limitations of their study, including the lack of strong data on environmental factors like smoking and cardiovascular disease, and a lack of the high-density single nucleotide polymorphisms data required to assign haplotypes.
Sohn EH, Han IC, Roos BR, et al. Genetic association between mmp9 and choroidal neovascularization in age-related macular degeneration. Ophthalmol. Sci. Published online December 18, 2020. doi:10.1016/j.xops.2020.100002