Association of APOA5 and APOC3 genetic polymorphisms with severity of hypertriglyceridemia in patients with cutaneous T-Cell lymphoma treated with bexarotene

Importance: hypertriglyceridemia is the most frequent and limiting adverse effect of bexarotene therapy in cutaneous T-cell lymphoma (CTCL). Despite standard prophylactic measures, there is a wide variability in the severity of this complication, which could be associated with both genetic and envir...

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Autores: Cabello Zamora, Irene, Alia, Pedro, Pintó Sala, Xavier, Muniesa Montserrat, Cristina, Fernández de Misa, Ricardo, Peñate, Yerai, Morillo, Mercedes, Pérez-Ferriols, Amparo, Estrach Panella, Ma. Teresa (María Teresa), Izu, Rosa, Gallardo, F. (Fernando), Román, Concepción, Cervigón, Iván, Ortiz Brugués, Ariadna, Ortiz Romero, Pablo Luis, Servitje Bedate, Octavio
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2018
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/127512
Acceso en línea:https://hdl.handle.net/2445/127512
Access Level:acceso abierto
Palabra clave:Polimorfisme genètic
Triglicèrids
Efectes secundaris dels medicaments
Medicaments antineoplàstics
Càncer de pell
Genetic polymorphisms
Triglycerides
Drug side effects
Antineoplastic agents
Skin cancer
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spelling Association of APOA5 and APOC3 genetic polymorphisms with severity of hypertriglyceridemia in patients with cutaneous T-Cell lymphoma treated with bexaroteneCabello Zamora, IreneAlia, PedroPintó Sala, XavierMuniesa Montserrat, CristinaFernández de Misa, RicardoPeñate, YeraiMorillo, MercedesPérez-Ferriols, AmparoEstrach Panella, Ma. Teresa (María Teresa)Izu, RosaGallardo, F. (Fernando)Román, ConcepciónCervigón, IvánOrtiz Brugués, AriadnaOrtiz Romero, Pablo LuisServitje Bedate, OctavioPolimorfisme genèticTriglicèridsEfectes secundaris dels medicamentsMedicaments antineoplàsticsCàncer de pellGenetic polymorphismsTriglyceridesDrug side effectsAntineoplastic agentsSkin cancerImportance: hypertriglyceridemia is the most frequent and limiting adverse effect of bexarotene therapy in cutaneous T-cell lymphoma (CTCL). Despite standard prophylactic measures, there is a wide variability in the severity of this complication, which could be associated with both genetic and environmental factors. Objectives: to analyze the association between genetic polymorphisms of apolipoprotein genes APOA5, APOC3, and APOE and the severity of hypertriglyceridemia during bexarotene therapy and to optimize patient selection for bexarotene therapy based on adverse effect profile. Design, Setting, and Participants: this case series study was conducted in 12 university referral hospitals in Spain from September 17, 2014, to February 6, 2015. One hundred twenty-five patients with a confirmed diagnosis of CTCL who had received bexarotene therapy for at least 3 months were enrolled. Nine patients were excluded owing to missing analytic triglyceride level data, leaving a study group of 116 patients. Data on demographic and cardiovascular risk factor were collected, and a complete blood analysis, including lipid profile and genetic analysis from a saliva sample, was performed. Main Outcomes and Measures: primary outcomes were the maximal triglyceride levels reported in association with the minor alleles of the polymorphisms studied. Results: among 116 patients, the mean (SD) age was 61.2 (14.7) years, 69 (59.5%) were men, and 85 (73.2%) had mycosis fungoides, the most prevalent form of CTCL. During bexarotene therapy, 96 patients (82.7%) experienced hypertriglyceridemia, which was severe or extreme in 8 of these patients (8.3%). Patients who carried minor alleles of the polymorphisms did not show significant differences in baseline triglyceride concentrations. After bexarotene treatment, carriers of at least 1 of the 2 minor alleles of APOA5 c.-1131T>C and APOC3 c.*40C>G showed lower levels of triglycerides than noncarriers (mean [SD], 241.59 [169.91] vs 330.97 [169.03] mg/dL, respectively; P = .02). Conclusions and Relevance: these results indicate that the screening of APOA5 and APOC3 genotypes may be useful to estimate changes in triglyceride concentrations during bexarotene treatment in patients with CTCL and also to identify the best candidates for bexarotene therapy based on the expected adverse effect profile.American Medical Association2018info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/127512Articles publicats en revistes (Ciències Clíniques)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.1001/jamadermatol.2018.3679JAMA Dermatology, 2018, vol. 154, num. 12, p. 1424-1431https://doi.org/10.1001/jamadermatol.2018.3679(c) American Medical Association, 2018info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1275122026-05-27T06:46:51Z
dc.title.none.fl_str_mv Association of APOA5 and APOC3 genetic polymorphisms with severity of hypertriglyceridemia in patients with cutaneous T-Cell lymphoma treated with bexarotene
title Association of APOA5 and APOC3 genetic polymorphisms with severity of hypertriglyceridemia in patients with cutaneous T-Cell lymphoma treated with bexarotene
spellingShingle Association of APOA5 and APOC3 genetic polymorphisms with severity of hypertriglyceridemia in patients with cutaneous T-Cell lymphoma treated with bexarotene
Cabello Zamora, Irene
Polimorfisme genètic
Triglicèrids
Efectes secundaris dels medicaments
Medicaments antineoplàstics
Càncer de pell
Genetic polymorphisms
Triglycerides
Drug side effects
Antineoplastic agents
Skin cancer
title_short Association of APOA5 and APOC3 genetic polymorphisms with severity of hypertriglyceridemia in patients with cutaneous T-Cell lymphoma treated with bexarotene
title_full Association of APOA5 and APOC3 genetic polymorphisms with severity of hypertriglyceridemia in patients with cutaneous T-Cell lymphoma treated with bexarotene
title_fullStr Association of APOA5 and APOC3 genetic polymorphisms with severity of hypertriglyceridemia in patients with cutaneous T-Cell lymphoma treated with bexarotene
title_full_unstemmed Association of APOA5 and APOC3 genetic polymorphisms with severity of hypertriglyceridemia in patients with cutaneous T-Cell lymphoma treated with bexarotene
title_sort Association of APOA5 and APOC3 genetic polymorphisms with severity of hypertriglyceridemia in patients with cutaneous T-Cell lymphoma treated with bexarotene
dc.creator.none.fl_str_mv Cabello Zamora, Irene
Alia, Pedro
Pintó Sala, Xavier
Muniesa Montserrat, Cristina
Fernández de Misa, Ricardo
Peñate, Yerai
Morillo, Mercedes
Pérez-Ferriols, Amparo
Estrach Panella, Ma. Teresa (María Teresa)
Izu, Rosa
Gallardo, F. (Fernando)
Román, Concepción
Cervigón, Iván
Ortiz Brugués, Ariadna
Ortiz Romero, Pablo Luis
Servitje Bedate, Octavio
author Cabello Zamora, Irene
author_facet Cabello Zamora, Irene
Alia, Pedro
Pintó Sala, Xavier
Muniesa Montserrat, Cristina
Fernández de Misa, Ricardo
Peñate, Yerai
Morillo, Mercedes
Pérez-Ferriols, Amparo
Estrach Panella, Ma. Teresa (María Teresa)
Izu, Rosa
Gallardo, F. (Fernando)
Román, Concepción
Cervigón, Iván
Ortiz Brugués, Ariadna
Ortiz Romero, Pablo Luis
Servitje Bedate, Octavio
author_role author
author2 Alia, Pedro
Pintó Sala, Xavier
Muniesa Montserrat, Cristina
Fernández de Misa, Ricardo
Peñate, Yerai
Morillo, Mercedes
Pérez-Ferriols, Amparo
Estrach Panella, Ma. Teresa (María Teresa)
Izu, Rosa
Gallardo, F. (Fernando)
Román, Concepción
Cervigón, Iván
Ortiz Brugués, Ariadna
Ortiz Romero, Pablo Luis
Servitje Bedate, Octavio
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Polimorfisme genètic
Triglicèrids
Efectes secundaris dels medicaments
Medicaments antineoplàstics
Càncer de pell
Genetic polymorphisms
Triglycerides
Drug side effects
Antineoplastic agents
Skin cancer
topic Polimorfisme genètic
Triglicèrids
Efectes secundaris dels medicaments
Medicaments antineoplàstics
Càncer de pell
Genetic polymorphisms
Triglycerides
Drug side effects
Antineoplastic agents
Skin cancer
description Importance: hypertriglyceridemia is the most frequent and limiting adverse effect of bexarotene therapy in cutaneous T-cell lymphoma (CTCL). Despite standard prophylactic measures, there is a wide variability in the severity of this complication, which could be associated with both genetic and environmental factors. Objectives: to analyze the association between genetic polymorphisms of apolipoprotein genes APOA5, APOC3, and APOE and the severity of hypertriglyceridemia during bexarotene therapy and to optimize patient selection for bexarotene therapy based on adverse effect profile. Design, Setting, and Participants: this case series study was conducted in 12 university referral hospitals in Spain from September 17, 2014, to February 6, 2015. One hundred twenty-five patients with a confirmed diagnosis of CTCL who had received bexarotene therapy for at least 3 months were enrolled. Nine patients were excluded owing to missing analytic triglyceride level data, leaving a study group of 116 patients. Data on demographic and cardiovascular risk factor were collected, and a complete blood analysis, including lipid profile and genetic analysis from a saliva sample, was performed. Main Outcomes and Measures: primary outcomes were the maximal triglyceride levels reported in association with the minor alleles of the polymorphisms studied. Results: among 116 patients, the mean (SD) age was 61.2 (14.7) years, 69 (59.5%) were men, and 85 (73.2%) had mycosis fungoides, the most prevalent form of CTCL. During bexarotene therapy, 96 patients (82.7%) experienced hypertriglyceridemia, which was severe or extreme in 8 of these patients (8.3%). Patients who carried minor alleles of the polymorphisms did not show significant differences in baseline triglyceride concentrations. After bexarotene treatment, carriers of at least 1 of the 2 minor alleles of APOA5 c.-1131T>C and APOC3 c.*40C>G showed lower levels of triglycerides than noncarriers (mean [SD], 241.59 [169.91] vs 330.97 [169.03] mg/dL, respectively; P = .02). Conclusions and Relevance: these results indicate that the screening of APOA5 and APOC3 genotypes may be useful to estimate changes in triglyceride concentrations during bexarotene treatment in patients with CTCL and also to identify the best candidates for bexarotene therapy based on the expected adverse effect profile.
publishDate 2018
dc.date.none.fl_str_mv 2018
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/127512
url https://hdl.handle.net/2445/127512
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1001/jamadermatol.2018.3679
JAMA Dermatology, 2018, vol. 154, num. 12, p. 1424-1431
https://doi.org/10.1001/jamadermatol.2018.3679
dc.rights.none.fl_str_mv (c) American Medical Association, 2018
info:eu-repo/semantics/openAccess
rights_invalid_str_mv (c) American Medical Association, 2018
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv American Medical Association
publisher.none.fl_str_mv American Medical Association
dc.source.none.fl_str_mv Articles publicats en revistes (Ciències Clíniques)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
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repository.mail.fl_str_mv
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