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Genetic Modifiers and Phenotype of Duchenne Muscular Dystrophy: A Systematic Review and Meta-Analysis
The transforming growth factor beta (TGFβ) pathway could modulate the Duchenne muscular dystrophy (DMD) phenotype. This meta-analysis aims to estimate the association of genetic variants involved in the TGFβ pathway, including the latent transforming growth factor beta binding protein 4 (LTBP4) and...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8401629/ https://www.ncbi.nlm.nih.gov/pubmed/34451895 http://dx.doi.org/10.3390/ph14080798 |
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author | Pascual-Morena, Carlos Cavero-Redondo, Iván Saz-Lara, Alicia Sequí-Domínguez, Irene Lucerón-Lucas-Torres, Maribel Martínez-Vizcaíno, Vicente |
author_facet | Pascual-Morena, Carlos Cavero-Redondo, Iván Saz-Lara, Alicia Sequí-Domínguez, Irene Lucerón-Lucas-Torres, Maribel Martínez-Vizcaíno, Vicente |
author_sort | Pascual-Morena, Carlos |
collection | PubMed |
description | The transforming growth factor beta (TGFβ) pathway could modulate the Duchenne muscular dystrophy (DMD) phenotype. This meta-analysis aims to estimate the association of genetic variants involved in the TGFβ pathway, including the latent transforming growth factor beta binding protein 4 (LTBP4) and secreted phosphoprotein 1 (SPP1) genes, among others, with age of loss of ambulation (LoA) and cardiac function in patients with DMD. Meta-analyses were conducted for the hazard ratio (HR) of LoA for each genetic variant. A subgroup analysis was performed in patients treated exclusively with glucocorticoids. Eight studies were included in the systematic review and four in the meta-analyses. The systematic review suggests a protective effect of LTBP4 haplotype IAAM (recessive model) for LoA. It is also suggested that the SPP1 rs28357094 genotype G (dominant model) is associated with early LoA in glucocorticoids-treated patients. The meta-analysis of the LTBP4 haplotype IAAM showed a protective association with LoA, with an HR = 0.78 (95% CI: 0.67–0.90). No association with LoA was observed for the SPP1 rs28357094. The LTBP4 haplotype IAAM is associated with a later LoA, especially in the Caucasian population, while the SPP1 rs28357094 genotype G could be associated with a poor response to glucocorticoids. Future research is suggested for SPP1 rs11730582, LTBP4 rs710160, and THBS1 rs2725797. |
format | Online Article Text |
id | pubmed-8401629 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-84016292021-08-29 Genetic Modifiers and Phenotype of Duchenne Muscular Dystrophy: A Systematic Review and Meta-Analysis Pascual-Morena, Carlos Cavero-Redondo, Iván Saz-Lara, Alicia Sequí-Domínguez, Irene Lucerón-Lucas-Torres, Maribel Martínez-Vizcaíno, Vicente Pharmaceuticals (Basel) Review The transforming growth factor beta (TGFβ) pathway could modulate the Duchenne muscular dystrophy (DMD) phenotype. This meta-analysis aims to estimate the association of genetic variants involved in the TGFβ pathway, including the latent transforming growth factor beta binding protein 4 (LTBP4) and secreted phosphoprotein 1 (SPP1) genes, among others, with age of loss of ambulation (LoA) and cardiac function in patients with DMD. Meta-analyses were conducted for the hazard ratio (HR) of LoA for each genetic variant. A subgroup analysis was performed in patients treated exclusively with glucocorticoids. Eight studies were included in the systematic review and four in the meta-analyses. The systematic review suggests a protective effect of LTBP4 haplotype IAAM (recessive model) for LoA. It is also suggested that the SPP1 rs28357094 genotype G (dominant model) is associated with early LoA in glucocorticoids-treated patients. The meta-analysis of the LTBP4 haplotype IAAM showed a protective association with LoA, with an HR = 0.78 (95% CI: 0.67–0.90). No association with LoA was observed for the SPP1 rs28357094. The LTBP4 haplotype IAAM is associated with a later LoA, especially in the Caucasian population, while the SPP1 rs28357094 genotype G could be associated with a poor response to glucocorticoids. Future research is suggested for SPP1 rs11730582, LTBP4 rs710160, and THBS1 rs2725797. MDPI 2021-08-13 /pmc/articles/PMC8401629/ /pubmed/34451895 http://dx.doi.org/10.3390/ph14080798 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Pascual-Morena, Carlos Cavero-Redondo, Iván Saz-Lara, Alicia Sequí-Domínguez, Irene Lucerón-Lucas-Torres, Maribel Martínez-Vizcaíno, Vicente Genetic Modifiers and Phenotype of Duchenne Muscular Dystrophy: A Systematic Review and Meta-Analysis |
title | Genetic Modifiers and Phenotype of Duchenne Muscular Dystrophy: A Systematic Review and Meta-Analysis |
title_full | Genetic Modifiers and Phenotype of Duchenne Muscular Dystrophy: A Systematic Review and Meta-Analysis |
title_fullStr | Genetic Modifiers and Phenotype of Duchenne Muscular Dystrophy: A Systematic Review and Meta-Analysis |
title_full_unstemmed | Genetic Modifiers and Phenotype of Duchenne Muscular Dystrophy: A Systematic Review and Meta-Analysis |
title_short | Genetic Modifiers and Phenotype of Duchenne Muscular Dystrophy: A Systematic Review and Meta-Analysis |
title_sort | genetic modifiers and phenotype of duchenne muscular dystrophy: a systematic review and meta-analysis |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8401629/ https://www.ncbi.nlm.nih.gov/pubmed/34451895 http://dx.doi.org/10.3390/ph14080798 |
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