Abstract
<b><i>Aim:</i></b> This study aimed to investigate the role of functionally significant polymorphisms of the <i>MMP1, MMP3,</i> and <i>MMP9</i> genes in the development of exfoliation glaucoma (XFG) in the Caucasian population of Central Russia. <b><i>Methods:</i></b> The study sample consisted of 724 participants, including 328 patients with XFG and 396 individuals in the control group. The participants were of Russian ethnicity (self-reported) born in Central Russia. The participants were genotyped at 8 functionally significant polymorphisms of the <i>MMP</i> genes (rs3918242, rs3918249, rs17576, rs3787268, rs2250889, rs17577 <i>MMP9,</i> rs679620 <i>MMP3</i>, and rs1799750 <i>MMP1</i>). The association analysis was performed using logistic regression. Two polymorphisms, which were associated with XFG, and 12 polymorphisms linked to them (<i>r</i><sup>2</sup> ≥ 0.8) were analyzed for their functional significance in silico. <b><i>Results:</i></b> Allele C of rs3918249 <i>MMP9</i> was associated with XFG according to the additive model (OR = 0.75, 95% CI: 0.56–0.93, <i>p</i><sub>perm</sub> = 0.015), and allele G of the rs2250889 <i>MMP9</i> locus was associated with XFG according to the additive (OR = 1.59, 95% CI: 1.10–2.29, <i>p</i><sub>perm</sub> = 0.013) and dominant (OR = 1.68, 95% CI: 1.11–2.56, <i>p</i><sub>perm</sub> = 0.016) models. Two XFG-associated loci of the <i>MMP9</i> gene and 12 SNPs linked to them had a significant regulatory potential (they are located in the evolutionarily conserved regions, promoter and enhancer histone marks, the DNAase-hypersensitivity regions, a region binding to regulatory protein, and a region of regulatory motifs) and may influence the expression of 13 genes and alternative splicing of 4 genes in various tissues and organs related to the pathogenesis of XFG. <b><i>Conclusion:</i></b> Allele C rs3918249 <i>MMP9</i> decreased risk for XFG (OR = 0.75), and allele G of the rs2250889 <i>MMP9</i> locus increased risk for XFG (OR = 1.59–1.68) in the Caucasian population of Central Russia.
Subject
Cellular and Molecular Neuroscience,Sensory Systems,Ophthalmology,General Medicine
Reference23 articles.
1. Quigley HA, Broman AT. The number of people with glaucoma worldwide in 2010 and 2020. Br J Ophthalmol. 2006;90(3):262–7.
2. Heijl A, Bengtsson B, Hyman L, Leske MC. Natural history of open-angle glaucoma. Ophthalmology. 2009;116(12):2271–6.
3. Ritch R, Schlötzer-Schrehardt U, Konstas AG. Why is glaucoma associated with exfoliation syndrome? Prog Retin Eye Res. 2003;22(3):253–75.
4. Schlötzer-Schrehardt U, Naumann GO. Ocular and systemic pseudoexfoliation syndrome. Am J Ophthalmol. 2006;141(5):921–37.
5. Rasmussen CA, Kaufman PL. The trabecular meshwork in normal eyes and in exfoliation glaucoma. J Glaucoma. 2014;23(8 Suppl 1):S15–9.