Association of Matrix Metalloproteinases Polymorphisms with Glaucoma Risk, Glaucoma Phenotype, and Response to Treatment with Selective Laser Trabeculoplasty or Latanoprost

Abstract

In open-angle glaucoma, the increase in intraocular pressure (IOP) is caused by an increased resistance to aqueous humour outflow in the trabecular meshwork. Since genetic variability of matrix metalloproteinase (MMP) genes may influence extracellular matrix remodelling, we investigated their association with glaucoma risk and/or response to treatment. The retrospective part of the study included patients with primary open-angle glaucoma and ocular hypertension (OHT); in the prospective part of the study, newly diagnosed patients with POAG or OHT were randomised to receive either latanoprost or selective laser trabeculoplasty (SLT) as the initial treatment. The reduction in IOP was measured 6 weeks after treatment. The following MMP single nucleotide polymorphisms were genotyped: MMP2 rs243865, rs243849, and rs7201; MMP3 rs3025058; MMP9 rs17576, rs17577, rs20544, and rs2250889; MMP14 rs1042704, rs1042704, and rs743257. Logistic regression was used to calculate odds ratios to assess the association between MMP polymorphism and risk of POAG or OHT, glaucoma phenotypes and response to treatment. Only carriers of the MMP3 rs3025058 TT genotype had a significantly higher risk of OHT, more advanced glaucoma, and a higher C/D ratio in the additive and dominant models. None of the investigated MMP polymorphisms were associated with response to treatment with latanoprost and SLT in our study population.

Keywords: glaucoma; latanoprost; matrix metalloproteinases; selective laser trabeculoplasty; single nucleotide polymorphisms.