Association between SNPs of Metalloproteinases and Prostaglandin F2α Receptor Genes and Latanoprost Response in Open-Angle Glaucoma

Purpose: To determine whether single nucleotide polymorphisms (SNPs) of genes coding for matrix metalloproteinases (MMPs) and the prostaglandin F2 alpha receptor gene (PTGFR) are related to a response to latanoprost in a white Spanish population of glaucomatous patients. Design: Caseecontrol study. Participants: One hundred twenty-four patients with open-angle glaucoma. Methods: Genotyping was performed in 117 patients with primary open-angle glaucoma with a minimum treatment duration of 4 weeks. Candidate genes and individual polymorphisms were selected according to the effect on the mechanism of action of latanoprost. Multi-SNP haplotype analyses for associations also were tested. Main Outcome Measures: Diurnal intraocular pressure reduction and genotyping of the SNPs in the MMPs and PTGFR. Results: The PTGFR SNPs were associated with positive (rs6686438, rs10786455) and negative (rs3753380, rs6672484, rs11578155) responses to latanoprost. Multiple testing found 2 genes, PTGFR and MMP-1, were related to refractoriness to latanoprost. Conclusions: The SNPs of the PTGFR and MMP-1 genes may determine the latanoprost response in a white European Spanish population. This study identified 5 SNPs related to the latanoprost response; 1 SNP, rs3753380, already has been associated with a poor response to latanoprost in a healthy Japanese population. Latanoprost is a commonly used antiglaucomatous drug, and increased knowledge of its mechanism of action will lead to advances in pharmacogenetics. (C) 2015 by the American Academy of Ophthalmology.