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Dissection of Clinical and Gene Expression Signatures of Familial versus Multifactorial Chylomicronemia
Familial chylomicronemia syndrome (FCS) is a rare disorder associated with chylomicronemia (CM) and an increased risk of pancreatitis. Most individuals with CM do not have FCS but exhibit multifactorial CM (MCM), which differs from FCS in terms of risk and disease management. This study aimed to inv...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7278277/ https://www.ncbi.nlm.nih.gov/pubmed/32537545 http://dx.doi.org/10.1210/jendso/bvaa056 |
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author | Tremblay, Karine Gaudet, Daniel Khoury, Etienne Brisson, Diane |
author_facet | Tremblay, Karine Gaudet, Daniel Khoury, Etienne Brisson, Diane |
author_sort | Tremblay, Karine |
collection | PubMed |
description | Familial chylomicronemia syndrome (FCS) is a rare disorder associated with chylomicronemia (CM) and an increased risk of pancreatitis. Most individuals with CM do not have FCS but exhibit multifactorial CM (MCM), which differs from FCS in terms of risk and disease management. This study aimed to investigate clinical and gene expression profiles of FCS and MCM patients. Anthropometrics, clinical, and biochemical variables were analyzed in 57 FCS and 353 MCM patients. Gene expression analyses were performed in a subsample of 19 FCS, 28 MCM, and 15 normolipidemic controls. Receiver operating characteristic (ROC) curve analyses were performed to analyze the capacity of variables to discriminate FCS from MCM. Sustained fasting triglycerides ≥20 mmol/L (>15 mmol/L with eruptive xanthomas), history of pancreatitis, poor response to fibrates, diagnosis of CM at childhood, body mass index <22 kg/m(2), and delipidated apolipoprotein B or glycerol levels <0.9 g/L and <0.05 mmol/L, respectively, had an area under the ROC curve ≥0.7. Gene expression analyses identified 142 probes differentially expressed in FCS and 32 in MCM compared with controls. Among them, 13 probes are shared between FCS and MCM; 63 are specific to FCS and 2 to MCM. Most FCS-specific or shared biomarkers are involved in inflammatory, immune, circadian, postprandial metabolism, signaling, docking systems, or receptor-mediated clearance mechanisms. This study reveals differential signatures of FCS and MCM. It opens the door to the identification of key mechanisms of CM expression and potential targets for the development of new treatments. |
format | Online Article Text |
id | pubmed-7278277 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-72782772020-06-12 Dissection of Clinical and Gene Expression Signatures of Familial versus Multifactorial Chylomicronemia Tremblay, Karine Gaudet, Daniel Khoury, Etienne Brisson, Diane J Endocr Soc Brief Report Familial chylomicronemia syndrome (FCS) is a rare disorder associated with chylomicronemia (CM) and an increased risk of pancreatitis. Most individuals with CM do not have FCS but exhibit multifactorial CM (MCM), which differs from FCS in terms of risk and disease management. This study aimed to investigate clinical and gene expression profiles of FCS and MCM patients. Anthropometrics, clinical, and biochemical variables were analyzed in 57 FCS and 353 MCM patients. Gene expression analyses were performed in a subsample of 19 FCS, 28 MCM, and 15 normolipidemic controls. Receiver operating characteristic (ROC) curve analyses were performed to analyze the capacity of variables to discriminate FCS from MCM. Sustained fasting triglycerides ≥20 mmol/L (>15 mmol/L with eruptive xanthomas), history of pancreatitis, poor response to fibrates, diagnosis of CM at childhood, body mass index <22 kg/m(2), and delipidated apolipoprotein B or glycerol levels <0.9 g/L and <0.05 mmol/L, respectively, had an area under the ROC curve ≥0.7. Gene expression analyses identified 142 probes differentially expressed in FCS and 32 in MCM compared with controls. Among them, 13 probes are shared between FCS and MCM; 63 are specific to FCS and 2 to MCM. Most FCS-specific or shared biomarkers are involved in inflammatory, immune, circadian, postprandial metabolism, signaling, docking systems, or receptor-mediated clearance mechanisms. This study reveals differential signatures of FCS and MCM. It opens the door to the identification of key mechanisms of CM expression and potential targets for the development of new treatments. Oxford University Press 2020-05-15 /pmc/articles/PMC7278277/ /pubmed/32537545 http://dx.doi.org/10.1210/jendso/bvaa056 Text en © Endocrine Society 2020. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Brief Report Tremblay, Karine Gaudet, Daniel Khoury, Etienne Brisson, Diane Dissection of Clinical and Gene Expression Signatures of Familial versus Multifactorial Chylomicronemia |
title | Dissection of Clinical and Gene Expression Signatures of Familial versus Multifactorial Chylomicronemia |
title_full | Dissection of Clinical and Gene Expression Signatures of Familial versus Multifactorial Chylomicronemia |
title_fullStr | Dissection of Clinical and Gene Expression Signatures of Familial versus Multifactorial Chylomicronemia |
title_full_unstemmed | Dissection of Clinical and Gene Expression Signatures of Familial versus Multifactorial Chylomicronemia |
title_short | Dissection of Clinical and Gene Expression Signatures of Familial versus Multifactorial Chylomicronemia |
title_sort | dissection of clinical and gene expression signatures of familial versus multifactorial chylomicronemia |
topic | Brief Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7278277/ https://www.ncbi.nlm.nih.gov/pubmed/32537545 http://dx.doi.org/10.1210/jendso/bvaa056 |
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