MLIP genotype as a predictor of pharmacological response in primary open-angle glaucoma and ocular hypertension
Open Access
- 15 January 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in Scientific Reports
- Vol. 11 (1), 1-9
- https://doi.org/10.1038/s41598-020-80954-2
Abstract
Predicting the therapeutic response to ocular hypotensive drugs is crucial for the clinical treatment and management of glaucoma. Our aim was to identify a possible genetic contribution to the response to current pharmacological treatments of choice in a white Mediterranean population with primary open-angle glaucoma (POAG) or ocular hypertension (OH). We conducted a prospective, controlled, randomized, partial crossover study that included 151 patients of both genders, aged 18 years and older, diagnosed with and requiring pharmacological treatment for POAG or OH in one or both eyes. We sought to identify copy number variants (CNVs) associated with differences in pharmacological response, using a DNA pooling strategy of carefully phenotyped treatment responders and non-responders, treated for a minimum of 6 weeks with a beta-blocker (timolol maleate) and/or prostaglandin analog (latanoprost). Diurnal intraocular pressure reduction and comparative genome wide CNVs were analyzed. Our finding that copy number alleles of an intronic portion of the MLIP gene is a predictor of pharmacological response to beta blockers and prostaglandin analogs could be used as a biomarker to guide first-tier POAG and OH treatment. Our finding improves understanding of the genetic factors modulating pharmacological response in POAG and OH, and represents an important contribution to the establishment of a personalized approach to the treatment of glaucoma.This publication has 41 references indexed in Scilit:
- Genome-wide association study identifies seven novel susceptibility loci for primary open-angle glaucomaHuman Molecular Genetics, 2018
- Prediction of CYP2D6 phenotype from genotype across world populationsGenetics in Medicine, 2017
- Non-coding RNAs in Development and Disease: Background, Mechanisms, and Therapeutic ApproachesPhysiological Reviews, 2016
- Association between SNPs of Metalloproteinases and Prostaglandin F2α Receptor Genes and Latanoprost Response in Open-Angle GlaucomaOphthalmology, 2015
- Pharmacogenomics Knowledge for Personalized MedicineClinical Pharmacology & Therapeutics, 2012
- Genome-wide pooling approach identifies SPATA5 as a new susceptibility locus for alopecia areataEuropean Journal of Human Genetics, 2011
- Copy number variants in pharmacogenetic genesTrends in Molecular Medicine, 2011
- Genomewide Association Studies — Illuminating Biologic PathwaysThe New England Journal of Medicine, 2009
- Long non-coding RNAs: insights into functionsNature Reviews Genetics, 2009
- SNPassoc: an R package to perform whole genome association studiesBioinformatics, 2007