Role of matrix metalloproteinase‐9 gene polymorphisms in glaucoma: A hospital‐based study in Chinese patients

Abstract

Background Glaucoma is the irreversible vision loss and contributes second leading cause of blindness worldwide. Matrix metalloproteinase‐9 (MMP‐9) is involved with remodeling and destruction of extracellular matrix. Elevated MMP‐9 levels and various functional variants of MMP‐9 have been associated with glaucoma in different population. In the current investigation, we tested association of MMP‐9 common variants with different clinical categories of glaucoma in Chinese population. Materials and Methods We enrolled total of 396 glaucoma patients those reported to hospital comprising of 212 primary angle closure glaucoma (PACG) cases and 184 primary open‐angle glaucoma POAG patients. In addition, 329 normal individuals from similar geographical areas were enrolled as healthy controls. Five common single nucleotide polymorphisms (rs3918242, rs3918254, rs2250889, rs3918249, and rs17576) were genotyped by PCR‐RFLP. Plasma levels of MMP‐9 were quantified by ELISA. Results Heterozygotes (GC) and allele “G” for rs2250889 polymorphism were more frequent in PACG cases compared with healthy controls (GC: P < .0001, OR = 2.26; G: P < .0001, OR = 1.19). Similarly, heterozygous mutant and minor allele for rs3918242 polymorphism were more prevalent in POAG in comparison with healthy controls. Interestingly, distribution of rs17576 variant was statistically higher in both PACG and POAG cases than healthy controls. Furthermore, analysis of plasma MMP‐9 with MMP‐9 polymorphisms revealed significant association of rs2250889, rs3918242, and rs17576 with plasma levels of the protein. Conclusions MMP‐9 mutants are associated with elevated plasma MMP‐9 and predisposed to development of glaucoma.

Novel Data about Association of the Functionally Significant Polymorphisms of the <b><i>MMP9</i></b> Gene with Exfoliation Glaucoma in the Caucasian Population of Central Russia

“…Locus rs2250889 MMP9, which was determined in the present study as associated with XFG, was previously reported as a candidate for PACG [32,34]. Interestingly, that allele G of this locus was determined as a risk factor for both PACG and XFG (OR = 1.57-1.71).…”

“…Interestingly, that allele G of this locus was determined as a risk factor for both PACG and XFG (OR = 1.57-1.71). On the other hand, no association of this variant with primary openangle glaucoma was determined [32].…”

“…Until now, several studies have studied association of the rs3918249 MMP9 polymorphism with development of the primary angle closure glaucoma (PACG) and pri-mary open-angle glaucoma [28][29][30][31][32], and only one of them reported such association with PACG [28]. Besides, as was mentioned above, possible association of rs3918249 MMP9 with glaucoma was suggested by 2 meta-analyses [16,33].…”

Association of the functionally significant polymorphisms of the MMP9 gene with H. pylori-positive gastric ulcer in the Caucasian population of Central Russia

“…Due to their pleiotropism, polymorphisms of the MMP9 genes play a key role in multiple biological pathways and therefore have been implicated not only in peptic ulcer [ 13 , 73 , present study], but also in cardiovascular diseases [ 60 , 61 ] as well as a broad range of other disorders involving processes of synthesis and degradation of extracellular matrix: various cancers, including digestive [ 46 – 48 , 74 – 76 ], glaucoma [ 27 , 77 , 78 ], and others [ 79 – 82 ].…”

Dataset of allele and genotype frequencies of the three functionally significant polymorphisms of the MMP genes in Russian patients with primary open-angle glaucoma, essential hypertension and peptic ulcer

“…The dataset contains the raw data (supplementary Table), frequencies of alleles and genotypes ( Table 1 ) for three SNPs of two MMP genes (rs1799750 MMP1 , rs3918242 and rs17576 MMP9 ) in Russian patients diagnosed with POAG, EH, and PU. These polymorphisms were previously reported for their association with POAG, EH, and PU ( Table 2 ) [1] , [2] , [3] , [4] , [5] , [6] , [7] , [8] , [9] , [10] , [11] , [12] , [13] , [14] , [15] , [16] , [17] , [18] , [19] , [20] , [21] , [22] , [23] , [24] , [25] , [26] , [27] , [28] , [29] , [30] , [31] , [32] , [33] , [34] , [35] , [36] , [37] , [38] , [39] , [40] , [41] , [42] , [43] , [44] , [45] . The studied SNPs manifest the regulatory potential ( Table 3 ), which is evidenced by several eQTLs ( Table 4 ) and splicing QTLs ( Table 5 ).…”