Functionally significant polymorphisms of the MMP9 gene are associated with primary open-angle glaucoma in the population of Russia

Purpose The aim of this study was to investigate the role of functionally significant loci of the matrix metalloproteinases genes 1, 3, 9 (MMP1, MMP3, and MMP9) in the development of primary open-angle glaucoma (POAG) in Caucasians of the Central region of Russia. Methods In total 604 participants were recruited for the study, including 208 patients with POAG and 396 healthy controls. They were genotyped at eight single nucleotide polymorphisms (SNPs) of the three MMP genes. The association was analyzed using logistic and log-linear regression. POAG-associated loci and their proxies were in silico assessed for their functional prediction. Results Variant allele G*rs2250889 of MMP9 was significantly associated with higher risk of POAG (ORcov = 1.57-1.71). Haplotype CCA [rs3918242-rs3918249-rs17576] of the MMP9 gene was associated with lower risk of POAG (ORcov = 0.33). Allele A*rs3787268 of MMP9 was associated with the low intraocular pressure in the POAG patients (beta(cov) = -0.176 - -0.272), and so were haplotypes AA [rs17576-rs3787268] (beta(cov) = -0.577) and AAC [rs17576-rs3787268- rs2250889] (beta(cov) = -0.742) of the same gene, whereas allele 2G*rs1799750 of MMP1 was associated with the earlier onset of the disease (beta(cov) = -0.112 - -0.218). In silico analysis of the polymorphisms suggested the functionality of POAG-associated SNPs and their proxies (epigenetic potential, expression and alternative splicing effects for several genes). Conclusions The MMP9 gene polymorphisms are associated with POAG and intraocular pressure in POAG patients; rs1799750 of MMP1 was associated with the earlier age of manifestation of the disease symptoms.