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Preferential X Chromosome Inactivation as a Mechanism to Explain Female Preponderance in Myasthenia Gravis
Myasthenia gravis (MG) is a neuromuscular autoimmune disease characterized by prevalence in young women (3:1). Several mechanisms proposed as explanations for gender bias, including skewed X chromosome inactivation (XCI) and dosage or sex hormones, are often involved in the development of autoimmuni...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9031138/ https://www.ncbi.nlm.nih.gov/pubmed/35456502 http://dx.doi.org/10.3390/genes13040696 |
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author | Nicolì, Vanessa Tabano, Silvia Maria Colapietro, Patrizia Maestri, Michelangelo Ricciardi, Roberta Stoccoro, Andrea Fontana, Laura Guida, Melania Miozzo, Monica Coppedè, Fabio Migliore, Lucia |
author_facet | Nicolì, Vanessa Tabano, Silvia Maria Colapietro, Patrizia Maestri, Michelangelo Ricciardi, Roberta Stoccoro, Andrea Fontana, Laura Guida, Melania Miozzo, Monica Coppedè, Fabio Migliore, Lucia |
author_sort | Nicolì, Vanessa |
collection | PubMed |
description | Myasthenia gravis (MG) is a neuromuscular autoimmune disease characterized by prevalence in young women (3:1). Several mechanisms proposed as explanations for gender bias, including skewed X chromosome inactivation (XCI) and dosage or sex hormones, are often involved in the development of autoimmunity. The skewed XCI pattern can lead to an unbalanced expression of some X-linked genes, as observed in several autoimmune disorders characterized by female predominance. No data are yet available regarding XCI and MG. We hypothesize that the preferential XCI pattern may contribute to the female bias observed in the onset of MG, especially among younger women. XCI analysis was performed on blood samples of 284 women between the ages of 20 and 82. XCI was tested using the Human Androgen Receptor Assay (HUMARA). XCI patterns were classified as random (XCI < 75%) and preferential (XCI ≥ 75%). In 121 informative patients, the frequency of skewed XCI patterns was 47%, significantly higher than in healthy controls (17%; p ≤ 0.00001). Interestingly, the phenomenon was observed mainly in younger patients (<45 years; p ≤ 0.00001). Furthermore, considering the XCI pattern and the other clinical characteristics of patients, no significant differences were found. In conclusion, we observed preferential XCI in MG female patients, suggesting its potential role in the aetiology of MG, as observed in other autoimmune diseases in women. |
format | Online Article Text |
id | pubmed-9031138 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-90311382022-04-23 Preferential X Chromosome Inactivation as a Mechanism to Explain Female Preponderance in Myasthenia Gravis Nicolì, Vanessa Tabano, Silvia Maria Colapietro, Patrizia Maestri, Michelangelo Ricciardi, Roberta Stoccoro, Andrea Fontana, Laura Guida, Melania Miozzo, Monica Coppedè, Fabio Migliore, Lucia Genes (Basel) Article Myasthenia gravis (MG) is a neuromuscular autoimmune disease characterized by prevalence in young women (3:1). Several mechanisms proposed as explanations for gender bias, including skewed X chromosome inactivation (XCI) and dosage or sex hormones, are often involved in the development of autoimmunity. The skewed XCI pattern can lead to an unbalanced expression of some X-linked genes, as observed in several autoimmune disorders characterized by female predominance. No data are yet available regarding XCI and MG. We hypothesize that the preferential XCI pattern may contribute to the female bias observed in the onset of MG, especially among younger women. XCI analysis was performed on blood samples of 284 women between the ages of 20 and 82. XCI was tested using the Human Androgen Receptor Assay (HUMARA). XCI patterns were classified as random (XCI < 75%) and preferential (XCI ≥ 75%). In 121 informative patients, the frequency of skewed XCI patterns was 47%, significantly higher than in healthy controls (17%; p ≤ 0.00001). Interestingly, the phenomenon was observed mainly in younger patients (<45 years; p ≤ 0.00001). Furthermore, considering the XCI pattern and the other clinical characteristics of patients, no significant differences were found. In conclusion, we observed preferential XCI in MG female patients, suggesting its potential role in the aetiology of MG, as observed in other autoimmune diseases in women. MDPI 2022-04-15 /pmc/articles/PMC9031138/ /pubmed/35456502 http://dx.doi.org/10.3390/genes13040696 Text en © 2022 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 | Article Nicolì, Vanessa Tabano, Silvia Maria Colapietro, Patrizia Maestri, Michelangelo Ricciardi, Roberta Stoccoro, Andrea Fontana, Laura Guida, Melania Miozzo, Monica Coppedè, Fabio Migliore, Lucia Preferential X Chromosome Inactivation as a Mechanism to Explain Female Preponderance in Myasthenia Gravis |
title | Preferential X Chromosome Inactivation as a Mechanism to Explain Female Preponderance in Myasthenia Gravis |
title_full | Preferential X Chromosome Inactivation as a Mechanism to Explain Female Preponderance in Myasthenia Gravis |
title_fullStr | Preferential X Chromosome Inactivation as a Mechanism to Explain Female Preponderance in Myasthenia Gravis |
title_full_unstemmed | Preferential X Chromosome Inactivation as a Mechanism to Explain Female Preponderance in Myasthenia Gravis |
title_short | Preferential X Chromosome Inactivation as a Mechanism to Explain Female Preponderance in Myasthenia Gravis |
title_sort | preferential x chromosome inactivation as a mechanism to explain female preponderance in myasthenia gravis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9031138/ https://www.ncbi.nlm.nih.gov/pubmed/35456502 http://dx.doi.org/10.3390/genes13040696 |
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