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

Ophthalmology. 2015 May;122(5):1040-8.e4. doi: 10.1016/j.ophtha.2014.12.038. Epub 2015 Feb 19.

Abstract

Purpose: To determine whether single nucleotide polymorphisms (SNPs) of genes coding for matrix metalloproteinases (MMPs) and the prostaglandin F2α receptor gene (PTGFR) are related to a response to latanoprost in a white Spanish population of glaucomatous patients.

Design: Case-control 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.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antihypertensive Agents / therapeutic use*
  • Case-Control Studies
  • Female
  • Genotyping Techniques
  • Glaucoma, Open-Angle / drug therapy*
  • Glaucoma, Open-Angle / genetics*
  • Humans
  • Intraocular Pressure / drug effects
  • Latanoprost
  • Male
  • Matrix Metalloproteinase 1 / genetics*
  • Matrix Metalloproteinases / genetics
  • Middle Aged
  • Polymerase Chain Reaction
  • Polymorphism, Single Nucleotide*
  • Prostaglandins F, Synthetic / therapeutic use*
  • Receptors, Prostaglandin / genetics*

Substances

  • Antihypertensive Agents
  • Prostaglandins F, Synthetic
  • Receptors, Prostaglandin
  • prostaglandin F2alpha receptor
  • Latanoprost
  • Matrix Metalloproteinases
  • MMP1 protein, human
  • Matrix Metalloproteinase 1