MLIP genotype as a predictor of pharmacological response in primary open-angle glaucoma and ocular hypertension
Canut, Maria Isabel (Centre d'Oftalmologia Barraquer (Barcelona, Catalunya))
Villa, O. (Quantitative Genomic Medicine Laboratories (qGenomics))
Kudsieh, B. (Hospital Universitario Puerta de Hierro Majadahonda (Madrid))
Mattlin, H. (Quantitative Genomic Medicine Laboratories (qGenomics))
Banchs, I. (Quantitative Genomic Medicine Laboratories (qGenomics))
González, J.R. (Universitat Pompeu Fabra)
Armengol, Lluís (Quantitative Genomic Medicine Laboratories (qGenomics))
Casaroli-Marano, Ricardo Pedro (Institut d'Investigació Biomèdica Sant Pau)
Universitat Autònoma de Barcelona

Fecha:	2021
Resumen:	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.
Ayudas:	Ministerio de Ciencia e Innovación PTQ-11-04953
Nota:	Altres ajuts: Fondo Europeo de Desarrollo Regional (FEDER)
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Adrenergic beta-Antagonists ; Adult ; Aged ; Alleles ; Biomarkers ; Co-Repressor Proteins ; Cross-Over Studies ; DNA Copy Number Variations ; Female ; Genome-Wide Association Study ; Genotype ; Glaucoma, Open-Angle ; Humans ; Intraocular Pressure ; Latanoprost ; Male ; Middle Aged ; Ocular Hypertension ; Prospective Studies ; Timolol
Publicado en:	Scientific reports, Vol. 11 Núm. 1 (december 2021) , p. 1583, ISSN 2045-2322

DOI: 10.1038/s41598-020-80954-2
PMID: 33452295

9 p, 1.1 MB

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Documentos de investigación > Documentos de los grupos de investigación de la UAB > Centros y grupos de investigación (producción científica) > Ciencias de la salud y biociencias > Institut de Recerca Sant Pau
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