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Association of the DNMT3B -579G>T Polymorphism with Risk of Thymomas in Patients with Myasthenia Gravis
Increasing evidence suggests a contribution of epigenetic processes in promoting cancer and autoimmunity. Myasthenia gravis (MG) is an autoimmune disease mediated, in approximately 80% of the patients, by antibodies against the nicotinic acetylcholine receptor (AChR+). Moreover, epithelial tumours (...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3834310/ https://www.ncbi.nlm.nih.gov/pubmed/24260492 http://dx.doi.org/10.1371/journal.pone.0080846 |
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author | Coppedè, Fabio Ricciardi, Roberta Denaro, Maria De Rosa, Anna Provenzano, Carlo Bartoccioni, Emanuela Baggiani, Angelo Lucchi, Marco Mussi, Alfredo Migliore, Lucia |
author_facet | Coppedè, Fabio Ricciardi, Roberta Denaro, Maria De Rosa, Anna Provenzano, Carlo Bartoccioni, Emanuela Baggiani, Angelo Lucchi, Marco Mussi, Alfredo Migliore, Lucia |
author_sort | Coppedè, Fabio |
collection | PubMed |
description | Increasing evidence suggests a contribution of epigenetic processes in promoting cancer and autoimmunity. Myasthenia gravis (MG) is an autoimmune disease mediated, in approximately 80% of the patients, by antibodies against the nicotinic acetylcholine receptor (AChR+). Moreover, epithelial tumours (thymomas) are present in about 10-20% of the patients, and there is indication that changes in DNA methylation might contribute to the risk and progression of thymomas. However, the role of epigenetics in MG is still not completely clarified. In the present study we investigated if a common polymorphism (-579G>T: rs1569686) in the promoter of the DNMT3B gene coding for the DNA methyltransferase 3B, an enzyme that mediates DNA methylation, increases the risk to develop MG or MG-associated thymomas. The study polymorphism was selected based on recent reports and a literature meta-analysis suggesting association with increased risk of various types of cancer. We screened 324 AChR+ MG patients (140 males and 184 females, mean age 56.0 ± 16.5 years) and 735 healthy matched controls (294 males and 441 females, mean age 57.3 ± 15.6 years). 94 of the total MG patients had a thymoma. While there was no association with the whole cohort of MG patients, we found a statistically significant association of the DNMT3B -579T allele (OR = 1.51; 95% CI=1.1-2.1, P = 0.01) and the TT homozygous genotype (OR = 2.59; 95% CI=1.4-4.9, P = 0.006) with the risk of thymoma. No association was observed in MG patients without thymoma, even after stratification into clinical subtypes. Present results suggest that the DNMT3B -579T allele might contribute to the risk of developing thymoma in MG patients, particularly in homozygous TT subjects. |
format | Online Article Text |
id | pubmed-3834310 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-38343102013-11-20 Association of the DNMT3B -579G>T Polymorphism with Risk of Thymomas in Patients with Myasthenia Gravis Coppedè, Fabio Ricciardi, Roberta Denaro, Maria De Rosa, Anna Provenzano, Carlo Bartoccioni, Emanuela Baggiani, Angelo Lucchi, Marco Mussi, Alfredo Migliore, Lucia PLoS One Research Article Increasing evidence suggests a contribution of epigenetic processes in promoting cancer and autoimmunity. Myasthenia gravis (MG) is an autoimmune disease mediated, in approximately 80% of the patients, by antibodies against the nicotinic acetylcholine receptor (AChR+). Moreover, epithelial tumours (thymomas) are present in about 10-20% of the patients, and there is indication that changes in DNA methylation might contribute to the risk and progression of thymomas. However, the role of epigenetics in MG is still not completely clarified. In the present study we investigated if a common polymorphism (-579G>T: rs1569686) in the promoter of the DNMT3B gene coding for the DNA methyltransferase 3B, an enzyme that mediates DNA methylation, increases the risk to develop MG or MG-associated thymomas. The study polymorphism was selected based on recent reports and a literature meta-analysis suggesting association with increased risk of various types of cancer. We screened 324 AChR+ MG patients (140 males and 184 females, mean age 56.0 ± 16.5 years) and 735 healthy matched controls (294 males and 441 females, mean age 57.3 ± 15.6 years). 94 of the total MG patients had a thymoma. While there was no association with the whole cohort of MG patients, we found a statistically significant association of the DNMT3B -579T allele (OR = 1.51; 95% CI=1.1-2.1, P = 0.01) and the TT homozygous genotype (OR = 2.59; 95% CI=1.4-4.9, P = 0.006) with the risk of thymoma. No association was observed in MG patients without thymoma, even after stratification into clinical subtypes. Present results suggest that the DNMT3B -579T allele might contribute to the risk of developing thymoma in MG patients, particularly in homozygous TT subjects. Public Library of Science 2013-11-19 /pmc/articles/PMC3834310/ /pubmed/24260492 http://dx.doi.org/10.1371/journal.pone.0080846 Text en © 2013 Coppedè 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, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Coppedè, Fabio Ricciardi, Roberta Denaro, Maria De Rosa, Anna Provenzano, Carlo Bartoccioni, Emanuela Baggiani, Angelo Lucchi, Marco Mussi, Alfredo Migliore, Lucia Association of the DNMT3B -579G>T Polymorphism with Risk of Thymomas in Patients with Myasthenia Gravis |
title | Association of the DNMT3B -579G>T Polymorphism with Risk of Thymomas in Patients with Myasthenia Gravis |
title_full | Association of the DNMT3B -579G>T Polymorphism with Risk of Thymomas in Patients with Myasthenia Gravis |
title_fullStr | Association of the DNMT3B -579G>T Polymorphism with Risk of Thymomas in Patients with Myasthenia Gravis |
title_full_unstemmed | Association of the DNMT3B -579G>T Polymorphism with Risk of Thymomas in Patients with Myasthenia Gravis |
title_short | Association of the DNMT3B -579G>T Polymorphism with Risk of Thymomas in Patients with Myasthenia Gravis |
title_sort | association of the dnmt3b -579g>t polymorphism with risk of thymomas in patients with myasthenia gravis |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3834310/ https://www.ncbi.nlm.nih.gov/pubmed/24260492 http://dx.doi.org/10.1371/journal.pone.0080846 |
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