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Role of matrix metalloproteinase-9 gene polymorphisms in glaucoma: A hospital-based study in Chinese patients
Fengqiong Zhao1, Zongshan Fan1, Xuewen Huang1
1Department of Ophthalmology, Nanchong Central Hospital, Nanchong, China.
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.
Insights
Common variants of matrix metalloproteinase-9 (MMP-9) are linked to glaucoma development in the Chinese population. Specific MMP-9 gene mutations correlate with elevated protein levels, increasing glaucoma risk.
Area of Science:
- Ophthalmology
- Genetics
- Biochemistry
Background:
- Glaucoma is a leading cause of irreversible blindness globally.
- Matrix metalloproteinase-9 (MMP-9) plays a role in extracellular matrix remodeling and has been implicated in glaucoma.
- Previous studies suggest associations between MMP-9 variants and glaucoma in various populations.
Purpose of the Study:
- To investigate the association of common MMP-9 gene variants with different clinical subtypes of glaucoma in the Chinese population.
- To determine if specific MMP-9 polymorphisms correlate with plasma MMP-9 levels.
Main Methods:
- Genotyping of five common MMP-9 single nucleotide polymorphisms (SNPs) using PCR-RFLP in 396 glaucoma patients (212 PACG, 184 POAG) and 329 healthy controls.
- Quantification of plasma MMP-9 levels using ELISA.
Main Results:
- The rs2250889 polymorphism (allele G) and rs17576 variant were significantly more frequent in both primary angle-closure glaucoma (PACG) and primary open-angle glaucoma (POAG) cases compared to controls.
- The rs3918242 polymorphism was more prevalent in POAG cases than in controls.
- Significant associations were found between MMP-9 polymorphisms (rs2250889, rs3918242, rs17576) and plasma MMP-9 levels.
Conclusions:
- Specific MMP-9 gene variants are associated with an increased risk of developing glaucoma in the Chinese population.
- These MMP-9 variants are linked to elevated plasma MMP-9 levels, suggesting a mechanism for glaucoma predisposition.
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