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The ACE I/D polymorphism does not explain heterogeneity of natural course and response to enzyme replacement therapy in Pompe disease
The majority of children and adults with Pompe disease in the population of European descent carry the leaky splicing GAA variant c.-32-13T>G (IVS1) in combination with a fully deleterious GAA variant on the second allele. The phenotypic spectrum of this patient group is exceptionally broad, with...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6285976/ https://www.ncbi.nlm.nih.gov/pubmed/30532252 http://dx.doi.org/10.1371/journal.pone.0208854 |
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author | Kuperus, Esther van der Meijden, Jan C. in ’t Groen, Stijn L. M. Kroos, Marian A. Hoogeveen-Westerveld, Marianne Rizopoulos, Dimitris Martinez, Monica Yasmin Nino Kruijshaar, Michelle E. van Doorn, Pieter A. van der Beek, Nadine A. M. E. van der Ploeg, Ans T. Pijnappel, W. W. M. Pim |
author_facet | Kuperus, Esther van der Meijden, Jan C. in ’t Groen, Stijn L. M. Kroos, Marian A. Hoogeveen-Westerveld, Marianne Rizopoulos, Dimitris Martinez, Monica Yasmin Nino Kruijshaar, Michelle E. van Doorn, Pieter A. van der Beek, Nadine A. M. E. van der Ploeg, Ans T. Pijnappel, W. W. M. Pim |
author_sort | Kuperus, Esther |
collection | PubMed |
description | The majority of children and adults with Pompe disease in the population of European descent carry the leaky splicing GAA variant c.-32-13T>G (IVS1) in combination with a fully deleterious GAA variant on the second allele. The phenotypic spectrum of this patient group is exceptionally broad, with symptom onset ranging from early infancy to late adulthood. In addition, the response to enzyme replacement therapy (ERT) varies between patients. The insertion/deletion (I/D) polymorphism of the angiotensin I-converting enzyme (ACE) has been suggested to be a modifier of disease onset and/or response to ERT. Here, we have investigated the effect of the ACE I/D polymorphism in a relatively large cohort of 131 children and adults with Pompe disease, of whom 112 were followed during treatment with ERT for 5 years. We assessed the use of wheelchair and mechanical ventilation, muscle strength assessed via manual muscle testing and hand-held dynamometry (HHD), distance walked on the six-minute walk test (6MWT), forced vital capacity (FVC) in sitting and supine position and daily-life activities assessed by R-PAct. Cross sectional analysis at first visit showed no differences between the genotypes with respect to age at first symptoms, diagnosis, wheelchair use, or ventilator use. Also response to ERT over 5 years assessed by linear mixed model analyses showed no significant differences between ACE groups for any of the outcome measures. The patient cohort contained 24 families with 54 siblings. Differences in ACE genotype could neither explain inter nor intra familial differences. We conclude that the ACE I/D polymorphism does not explain the large variation in disease severity and response to ERT observed among Pompe patients with the same c.-32-13T>G GAA variant. |
format | Online Article Text |
id | pubmed-6285976 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-62859762018-12-28 The ACE I/D polymorphism does not explain heterogeneity of natural course and response to enzyme replacement therapy in Pompe disease Kuperus, Esther van der Meijden, Jan C. in ’t Groen, Stijn L. M. Kroos, Marian A. Hoogeveen-Westerveld, Marianne Rizopoulos, Dimitris Martinez, Monica Yasmin Nino Kruijshaar, Michelle E. van Doorn, Pieter A. van der Beek, Nadine A. M. E. van der Ploeg, Ans T. Pijnappel, W. W. M. Pim PLoS One Research Article The majority of children and adults with Pompe disease in the population of European descent carry the leaky splicing GAA variant c.-32-13T>G (IVS1) in combination with a fully deleterious GAA variant on the second allele. The phenotypic spectrum of this patient group is exceptionally broad, with symptom onset ranging from early infancy to late adulthood. In addition, the response to enzyme replacement therapy (ERT) varies between patients. The insertion/deletion (I/D) polymorphism of the angiotensin I-converting enzyme (ACE) has been suggested to be a modifier of disease onset and/or response to ERT. Here, we have investigated the effect of the ACE I/D polymorphism in a relatively large cohort of 131 children and adults with Pompe disease, of whom 112 were followed during treatment with ERT for 5 years. We assessed the use of wheelchair and mechanical ventilation, muscle strength assessed via manual muscle testing and hand-held dynamometry (HHD), distance walked on the six-minute walk test (6MWT), forced vital capacity (FVC) in sitting and supine position and daily-life activities assessed by R-PAct. Cross sectional analysis at first visit showed no differences between the genotypes with respect to age at first symptoms, diagnosis, wheelchair use, or ventilator use. Also response to ERT over 5 years assessed by linear mixed model analyses showed no significant differences between ACE groups for any of the outcome measures. The patient cohort contained 24 families with 54 siblings. Differences in ACE genotype could neither explain inter nor intra familial differences. We conclude that the ACE I/D polymorphism does not explain the large variation in disease severity and response to ERT observed among Pompe patients with the same c.-32-13T>G GAA variant. Public Library of Science 2018-12-07 /pmc/articles/PMC6285976/ /pubmed/30532252 http://dx.doi.org/10.1371/journal.pone.0208854 Text en © 2018 Kuperus et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Kuperus, Esther van der Meijden, Jan C. in ’t Groen, Stijn L. M. Kroos, Marian A. Hoogeveen-Westerveld, Marianne Rizopoulos, Dimitris Martinez, Monica Yasmin Nino Kruijshaar, Michelle E. van Doorn, Pieter A. van der Beek, Nadine A. M. E. van der Ploeg, Ans T. Pijnappel, W. W. M. Pim The ACE I/D polymorphism does not explain heterogeneity of natural course and response to enzyme replacement therapy in Pompe disease |
title | The ACE I/D polymorphism does not explain heterogeneity of natural course and response to enzyme replacement therapy in Pompe disease |
title_full | The ACE I/D polymorphism does not explain heterogeneity of natural course and response to enzyme replacement therapy in Pompe disease |
title_fullStr | The ACE I/D polymorphism does not explain heterogeneity of natural course and response to enzyme replacement therapy in Pompe disease |
title_full_unstemmed | The ACE I/D polymorphism does not explain heterogeneity of natural course and response to enzyme replacement therapy in Pompe disease |
title_short | The ACE I/D polymorphism does not explain heterogeneity of natural course and response to enzyme replacement therapy in Pompe disease |
title_sort | ace i/d polymorphism does not explain heterogeneity of natural course and response to enzyme replacement therapy in pompe disease |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6285976/ https://www.ncbi.nlm.nih.gov/pubmed/30532252 http://dx.doi.org/10.1371/journal.pone.0208854 |
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