title: Association between SNPs of Metalloproteinases and Prostaglandin F2α Receptor Genes and Latanoprost Response in Open-Angle Glaucoma.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  Case-control study.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
authors.affiliation: Instituto de Oftalmobiologia Aplicada, IOBA, Universidad de Valladolid, Valladolid, Spain. Electronic address: ussa@ioba.med.uva.es.
authors.forename: Fernando
authors.initials: F
authors.lastname: Ussa
authors.affiliation: Instituto de Oftalmobiologia Aplicada, IOBA, Universidad de Valladolid, Valladolid, Spain.
authors.forename: Itziar
authors.initials: I
authors.lastname: Fernandez
authors.affiliation: Instituto de Investigacion Sanitaria de Santiago, Fundacion Publica Galega de Medicina Xenomica, SERGAS, Santiago de Compostela, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Brion
authors.affiliation: Instituto de Investigacion Sanitaria de Santiago, Fundacion Publica Galega de Medicina Xenomica, SERGAS, Santiago de Compostela, Spain; Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia.
authors.forename: Angel
authors.initials: A
authors.lastname: Carracedo
authors.affiliation: Instituto de Oftalmobiologia Aplicada, IOBA, Universidad de Valladolid, Valladolid, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Blazquez
authors.affiliation: Instituto de Oftalmobiologia Aplicada, IOBA, Universidad de Valladolid, Valladolid, Spain.
authors.forename: Maria T
authors.initials: MT
authors.lastname: Garcia
authors.affiliation: Hospital Universitario de Salamanca, Salamanca, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Sanchez-Jara
authors.affiliation: Hospital Universitario de Salamanca, Salamanca, Spain.
authors.forename: Lourdes
authors.initials: L
authors.lastname: De Juan-Marcos
authors.affiliation: Hospital Puerta del Mar, Cadiz, Spain.
authors.forename: Soledad
authors.initials: S
authors.lastname: Jimenez-Carmona
authors.affiliation: Instituto de Oftalmobiologia Aplicada, IOBA, Universidad de Valladolid, Valladolid, Spain; Hospital Clinico Universitario de Valladolid, Valladolid, Spain.
authors.forename: Jose R
authors.initials: JR
authors.lastname: Juberias
authors.affiliation: Hospital Clinico San Carlos, Madrid, Spain.
authors.forename: Jose M
authors.initials: JM
authors.lastname: Martinez-de-la-Casa
authors.affiliation: Instituto de Oftalmobiologia Aplicada, IOBA, Universidad de Valladolid, Valladolid, Spain; Hospital Clinico Universitario de Valladolid, Valladolid, Spain.
authors.forename: Jose C
authors.initials: JC
authors.lastname: Pastor
mesh_terms: D000368:Aged; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D016022:Case-Control Studies; D005260:Female; D060005:Genotyping Techniques; D005902:Glaucoma, Open-Angle / Q000188:drug therapy* / Q000235:genetics*; D006801:Humans; D007429:Intraocular Pressure / Q000187:drug effects; D000077338:Latanoprost; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000235:genetics*; D020782:Matrix Metalloproteinases / Q000235:genetics; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011461:Prostaglandins F, Synthetic / Q000627:therapeutic use*; D011982:Receptors, Prostaglandin / Q000235:genetics*
chemical_list: D000959:Antihypertensive Agents; D011461:Prostaglandins F, Synthetic; D011982:Receptors, Prostaglandin; C034671:prostaglandin F2alpha receptor; D000077338:Latanoprost; D020782:Matrix Metalloproteinases; C522360:MMP1 protein, human; D020781:Matrix Metalloproteinase 1