MLIP genotype as a predictor of pharmacological response in primary open-angle glaucoma and ocular hypertension

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 o...

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Autores: Canut, Maria Isabel, Villa, Olaya|||0000-0003-4672-4963, Kudsieh, Bachar|||0000-0002-2600-8233, Mattlin, Heidi, Banchs, Isabel, González, Juan Ramón|||0000-0003-3267-2146, Armengol, Lluís, Casaroli-Marano, Ricardo Pedro|||0000-0003-1812-9323
Tipo de recurso: artículo
Fecha de publicación:2021
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:269949
Acceso en línea:https://ddd.uab.cat/record/269949
https://dx.doi.org/urn:doi:10.1038/s41598-020-80954-2
Access Level:acceso abierto
Palabra clave: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
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network_acronym_str ES
network_name_str España
repository_id_str
spelling MLIP genotype as a predictor of pharmacological response in primary open-angle glaucoma and ocular hypertensionCanut, Maria IsabelVilla, Olaya|||0000-0003-4672-4963Kudsieh, Bachar|||0000-0002-2600-8233Mattlin, HeidiBanchs, IsabelGonzález, Juan Ramón|||0000-0003-3267-2146Armengol, LluísCasaroli-Marano, Ricardo Pedro|||0000-0003-1812-9323Adrenergic beta-AntagonistsAdultAgedAllelesBiomarkersCo-Repressor ProteinsCross-Over StudiesDNA Copy Number VariationsFemaleGenome-Wide Association StudyGenotypeGlaucoma, Open-AngleHumansIntraocular PressureLatanoprostMaleMiddle AgedOcular HypertensionProspective StudiesTimololPredicting 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.Universitat Autònoma de Barcelona 22021-01-0120212021-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/269949https://dx.doi.org/urn:doi:10.1038/s41598-020-80954-2reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengMinisterio de Ciencia e Innovación https://doi.org/10.13039/501100004837 PTQ-11-04953open accesshttp://purl.org/coar/access_right/c_abf2Aquest 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.https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:2699492026-06-06T12:50:31Z
dc.title.none.fl_str_mv MLIP genotype as a predictor of pharmacological response in primary open-angle glaucoma and ocular hypertension
title MLIP genotype as a predictor of pharmacological response in primary open-angle glaucoma and ocular hypertension
spellingShingle MLIP genotype as a predictor of pharmacological response in primary open-angle glaucoma and ocular hypertension
Canut, Maria Isabel
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
title_short MLIP genotype as a predictor of pharmacological response in primary open-angle glaucoma and ocular hypertension
title_full MLIP genotype as a predictor of pharmacological response in primary open-angle glaucoma and ocular hypertension
title_fullStr MLIP genotype as a predictor of pharmacological response in primary open-angle glaucoma and ocular hypertension
title_full_unstemmed MLIP genotype as a predictor of pharmacological response in primary open-angle glaucoma and ocular hypertension
title_sort MLIP genotype as a predictor of pharmacological response in primary open-angle glaucoma and ocular hypertension
dc.creator.none.fl_str_mv Canut, Maria Isabel
Villa, Olaya|||0000-0003-4672-4963
Kudsieh, Bachar|||0000-0002-2600-8233
Mattlin, Heidi
Banchs, Isabel
González, Juan Ramón|||0000-0003-3267-2146
Armengol, Lluís
Casaroli-Marano, Ricardo Pedro|||0000-0003-1812-9323
author Canut, Maria Isabel
author_facet Canut, Maria Isabel
Villa, Olaya|||0000-0003-4672-4963
Kudsieh, Bachar|||0000-0002-2600-8233
Mattlin, Heidi
Banchs, Isabel
González, Juan Ramón|||0000-0003-3267-2146
Armengol, Lluís
Casaroli-Marano, Ricardo Pedro|||0000-0003-1812-9323
author_role author
author2 Villa, Olaya|||0000-0003-4672-4963
Kudsieh, Bachar|||0000-0002-2600-8233
Mattlin, Heidi
Banchs, Isabel
González, Juan Ramón|||0000-0003-3267-2146
Armengol, Lluís
Casaroli-Marano, Ricardo Pedro|||0000-0003-1812-9323
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universitat Autònoma de Barcelona
dc.subject.none.fl_str_mv 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
topic 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
description 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.
publishDate 2021
dc.date.none.fl_str_mv 2
2021-01-01
2021
2021-01-01
dc.type.none.fl_str_mv Article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://ddd.uab.cat/record/269949
https://dx.doi.org/urn:doi:10.1038/s41598-020-80954-2
url https://ddd.uab.cat/record/269949
https://dx.doi.org/urn:doi:10.1038/s41598-020-80954-2
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv Ministerio de Ciencia e Innovación https://doi.org/10.13039/501100004837 PTQ-11-04953
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Dipòsit Digital de Documents de la UAB
instname:Universitat Autònoma de Barcelona
instname_str Universitat Autònoma de Barcelona
reponame_str Dipòsit Digital de Documents de la UAB
collection Dipòsit Digital de Documents de la UAB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,301603

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