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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...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
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.
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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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