Genetic association of -1562C>T polymorphism in the MMP9 gene with primary glaucoma in a north Indian population

Abstract

MMP (Matrix metalloproteinase) 9 is reported to affect glaucoma pathogenesis by altering intraocular pressure (IOP) through its role in remodeling the extracellular matrix (ECM) in the trabecular meshwork. A genetic variant at the promoter region in the MMP9 gene (-1562C>T) has a putative role in regulating its transcription rate and hence can affect genetic predisposition to primary glaucoma. The present study examined the association of -1562C>T promoter polymorphism in the MMP9 gene with Primary Open Angle Glaucoma (POAG) and Primary Angle Closure Glaucoma (PACG) in a north Indian population. A total of 729 subjects (POAG = 224, PACG = 138 and 367 controls) were recruited for the study. Genotyping for the promoter sequence variant was done with PCR-RFLP method. Genotypic and allelic frequency distribution of the POAG and PACG data sets were compared to that of controls by chi-square test and genetic association was tested under different genetic models as implemented under PLINK. Statistically significant difference was observed in the genotype frequencies between PACG cases and controls (p = 0.030). However, in the POAG cases, this difference was only borderline (p = 0.052). Genetic model analysis, under the dominant model revealed 1.6 and 1.4 fold increased susceptibility to PACG and POAG (p = 0.012, p = 0.032) respectively. A higher frequency of CT genotype was observed in PACG as well as POAG males as compared to female subjects. According to the dominant model, CT+TT genotype conferred 1.8 fold higher risk of developing PACG among male patients as compared to the control group (p = 0.048, OR = 1.87;1.00–3.50). Current findings suggest significant association of MMP9 -1562C>T polymorphism with primary glaucoma in the targeted north Indian population and warrant further replication of the findings in other populations.

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

“…Role of matrix metalloproteinase‐9 (MMP‐9) variants have been well investigated in different populations as MMP‐9 gene is responsible for remodeling of extracellular matrix. A recent study in North Indian patients showed 1.6 and 1.4 fold higher risk for development of PACG and POAG, respectively, in subject harbored with mutant for MMP‐9 (−1562 C > T) polymorphism . Meta‐analysis if earlier published reports revealed protective feature of rs17576 and rs3918249 variant against glaucoma development .…”

“…A recent study in North Indian patients showed 1.6 and 1.4 fold higher risk for development of PACG and POAG, respectively, in subject harbored with mutant for MMP-9 (−1562 C > T) polymorphism. 11 Meta-analysis if earlier published reports revealed protective feature of rs17576 and rs3918249 variant against glaucoma development. 12,13 In Han Chinese population, variants of rs3918254 were associated with susceptibility to PACG.…”

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 ).…”

Matrixmetalloproteinase-9 Genetic Variation with Cataract, Glaucoma and Retinoblastoma in a Senegalese Population

“…Awadalla, et al [20], describe in Caucasians an amino acid change (Arginine to Glutamine) responsible for protein expression of MMP9 favorable to glaucoma with SNPs rs17576 and rs3918249. In addition, Thakur, et al [21] highlight the relationship between the change in MMP9 activity in the retina, the optic nerve, the aqueous humor, the trabeculum and glaucoma in the human eye. In the Chinese, the most likely locus for angle-closure glaucoma is rs3918254.…”