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

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

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Sanger sequencing chromatograms for validation of genotypes.

<p>A) Homozygous CC genotype B) Heterozygous CT genotype C) Homozygous TT genotype.</p

Distribution of allele frequency, genotype frequency and genetic model of rs3918242 among PACG cases and controls.

<p>Distribution of allele frequency, genotype frequency and genetic model of rs3918242 among PACG cases and controls.</p

Gender wise comparison of PACG cases and controls.

<p>Gender wise comparison of PACG cases and controls.</p

Gender-wise comparison of POAG cases and controls.

<p>Gender-wise comparison of POAG cases and controls.</p

Digested PCR product of <i>MMP9</i> -1562C>T.

<p>Well1 = 100bp Ladder; S2,10,11,12 = Heterozygous (436/242/194bp); S1,3,4,5,6,7,8,9 = Homozygous wild (436bp); UD = Undigested PCR product.</p

Distribution of allele frequency, genotype frequency and genetic model of rs3918242 among POAG cases and controls.

<p>Distribution of allele frequency, genotype frequency and genetic model of rs3918242 among POAG cases and controls.</p

The genotype distribution of -1562C>T MMP9 gene polymorphisms in patients with open-angle glaucoma (POAG) and angle closure glaucoma (PACG) according to CDR and IOP.

<p>The genotype distribution of -1562C>T MMP9 gene polymorphisms in patients with open-angle glaucoma (POAG) and angle closure glaucoma (PACG) according to CDR and IOP.</p

Frequency distribution of males and females among POAG and PACG cases with respect to control subjects.

<p>Frequency distribution of males and females among POAG and PACG cases with respect to control subjects.</p