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Abstract #60508 Published in IGR 16-4

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

Ussa F; Fernandez I; Brion M; Carracedo A; Blazquez F; Garcia MT; Sanchez-Jara A; de Juan-Marcos L; Jimenez-Carmona S; Juberias JR; Martinez-de-la-Casa JM; Pastor JC
Ophthalmology 2015; 122: 1040-8.e4

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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.

Instituto de Oftalmobiologia Aplicada, IOBA, Universidad de Valladolid, Valladolid, Spain. Electronic address: ussa@ioba.med.uva.es.

Full article

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Classification:

11.4 Prostaglandins (Part of: 11 Medical treatment)
3.4.2 Gene studies (Part of: 3 Laboratory methods > 3.4 Molecular genetics)
3.5 Molecular biology incl. SiRNA (Part of: 3 Laboratory methods)

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