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<p>Abstract</p> <p>Background</p> <p>Trachoma, an infectious disease of the conjunctiva caused by <it>Chlamydia trachomatis</it>, is an important global cause of blindness. A dysregulated extracellular matrix (ECM) proteolysis during the processes of tissue repair following infection and inflammation are thought to play a key role in the development of fibrotic sequelae of infection, which ultimately leads to blindness. Expression and activity of matrix metalloproteinase 9 (MMP-9), a major effector of ECM turnover, is up-regulated in the inflamed conjunctiva of trachoma subjects. Genetic variation within the <it>MMP9 </it>gene affects <it>in vitro MMP9 </it>expression levels, enzymatic activity and susceptibility to various inflammatory and fibrotic conditions.</p> <p>Methods</p> <p>We genotyped 651 case-control pairs from trachoma endemic villages in The Gambia for coding single nucleotide polymorphisms (SNPs) in the <it>MMP9 </it>gene using the high-throughput Sequenom^®system. Single marker and haplotype conditional logistic regression (CLR) analysis for disease association was performed.</p> <p>Results</p> <p>The Q279R mutation located in exon 6 of <it>MMP9 </it>was found to be associated with lower risk for severe disease sequelae of ocular <it>Chlamydia trachomatis </it>infection. This mutation, which leads to a nonsynonymous amino-acid change within the active site of the enzyme may reduce MMP-9-induced degradation of the structural components of the ECM during inflammatory episodes in trachoma and its associated fibrosis.</p> <p>Conclusion</p> <p>This work supports the hypothesis that MMP-9 has a role in the pathogenesis of blinding trachoma.</p>