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Genetic Variants Associated with FDNY WTC-Related Sarcoidosis
Sarcoidosis is a systemic granulomatous disease of unknown etiology. It may develop in response to an exposure or inflammatory trigger in the background of a genetically primed abnormal immune response. Thus, genetic studies are potentially important to our understanding of the pathogenesis of sarco...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6572061/ https://www.ncbi.nlm.nih.gov/pubmed/31126090 http://dx.doi.org/10.3390/ijerph16101830 |
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author | Cleven, Krystal L. Ye, Kenny Zeig-Owens, Rachel Hena, Kerry M. Montagna, Cristina Shan, Jidong Hosgood, H. Dean Jaber, Nadia Weiden, Michael D. Colbeth, Hilary L. Goldfarb, David G. Spivack, Simon D. Prezant, David J. |
author_facet | Cleven, Krystal L. Ye, Kenny Zeig-Owens, Rachel Hena, Kerry M. Montagna, Cristina Shan, Jidong Hosgood, H. Dean Jaber, Nadia Weiden, Michael D. Colbeth, Hilary L. Goldfarb, David G. Spivack, Simon D. Prezant, David J. |
author_sort | Cleven, Krystal L. |
collection | PubMed |
description | Sarcoidosis is a systemic granulomatous disease of unknown etiology. It may develop in response to an exposure or inflammatory trigger in the background of a genetically primed abnormal immune response. Thus, genetic studies are potentially important to our understanding of the pathogenesis of sarcoidosis. We developed a case-control study which explored the genetic variations between firefighters in the Fire Department of the City of New York (FDNY) with World Trade Center (WTC)-related sarcoidosis and those with WTC exposure, but without sarcoidosis. The loci of fifty-one candidate genes related to granuloma formation, inflammation, immune response, and/or sarcoidosis were sequenced at high density in enhancer/promoter, exonic, and 5’ untranslated regions. Seventeen allele variants of human leukocyte antigen (HLA) and non-HLA genes were found to be associated with sarcoidosis, and all were within chromosomes 1 and 6. Our results also suggest an association between extrathoracic involvement and allele variants of HLA and non-HLA genes found not only on chromosomes 1 and 6, but also on chromosomes 16 and 17. We found similarities between genetic variants with WTC-related sarcoidosis and those reported previously in sporadic sarcoidosis cases within the general population. In addition, we identified several allele variants never previously reported in association with sarcoidosis. If confirmed in larger studies with known environmental exposures, these novel findings may provide insight into the gene-environment interactions key to the development of sarcoidosis. |
format | Online Article Text |
id | pubmed-6572061 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-65720612019-06-18 Genetic Variants Associated with FDNY WTC-Related Sarcoidosis Cleven, Krystal L. Ye, Kenny Zeig-Owens, Rachel Hena, Kerry M. Montagna, Cristina Shan, Jidong Hosgood, H. Dean Jaber, Nadia Weiden, Michael D. Colbeth, Hilary L. Goldfarb, David G. Spivack, Simon D. Prezant, David J. Int J Environ Res Public Health Article Sarcoidosis is a systemic granulomatous disease of unknown etiology. It may develop in response to an exposure or inflammatory trigger in the background of a genetically primed abnormal immune response. Thus, genetic studies are potentially important to our understanding of the pathogenesis of sarcoidosis. We developed a case-control study which explored the genetic variations between firefighters in the Fire Department of the City of New York (FDNY) with World Trade Center (WTC)-related sarcoidosis and those with WTC exposure, but without sarcoidosis. The loci of fifty-one candidate genes related to granuloma formation, inflammation, immune response, and/or sarcoidosis were sequenced at high density in enhancer/promoter, exonic, and 5’ untranslated regions. Seventeen allele variants of human leukocyte antigen (HLA) and non-HLA genes were found to be associated with sarcoidosis, and all were within chromosomes 1 and 6. Our results also suggest an association between extrathoracic involvement and allele variants of HLA and non-HLA genes found not only on chromosomes 1 and 6, but also on chromosomes 16 and 17. We found similarities between genetic variants with WTC-related sarcoidosis and those reported previously in sporadic sarcoidosis cases within the general population. In addition, we identified several allele variants never previously reported in association with sarcoidosis. If confirmed in larger studies with known environmental exposures, these novel findings may provide insight into the gene-environment interactions key to the development of sarcoidosis. MDPI 2019-05-23 2019-05 /pmc/articles/PMC6572061/ /pubmed/31126090 http://dx.doi.org/10.3390/ijerph16101830 Text en © 2019 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Cleven, Krystal L. Ye, Kenny Zeig-Owens, Rachel Hena, Kerry M. Montagna, Cristina Shan, Jidong Hosgood, H. Dean Jaber, Nadia Weiden, Michael D. Colbeth, Hilary L. Goldfarb, David G. Spivack, Simon D. Prezant, David J. Genetic Variants Associated with FDNY WTC-Related Sarcoidosis |
title | Genetic Variants Associated with FDNY WTC-Related Sarcoidosis |
title_full | Genetic Variants Associated with FDNY WTC-Related Sarcoidosis |
title_fullStr | Genetic Variants Associated with FDNY WTC-Related Sarcoidosis |
title_full_unstemmed | Genetic Variants Associated with FDNY WTC-Related Sarcoidosis |
title_short | Genetic Variants Associated with FDNY WTC-Related Sarcoidosis |
title_sort | genetic variants associated with fdny wtc-related sarcoidosis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6572061/ https://www.ncbi.nlm.nih.gov/pubmed/31126090 http://dx.doi.org/10.3390/ijerph16101830 |
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