Genetic Variants Associated with FDNY WTC-Related Sarcoidosis

Krystal L. Cleven, Qian K. Ye, Rachel Zeig-Owens, Kerry M. Hena, Cristina Montagna, Jidong Shan, Howard D. Hosgood, Nadia Jaber, Michael D. Weiden, Hilary L. Colbeth, David G. Goldfarb, Simon D. Spivack, David J. Prezant

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

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.

Original languageEnglish (US)
JournalInternational journal of environmental research and public health
Volume16
Issue number10
DOIs
StatePublished - May 23 2019

Fingerprint

Sarcoidosis
HLA Antigens
Chromosomes, Human, Pair 6
Chromosomes, Human, Pair 1
Alleles
Firefighters
Genes
Chromosomes, Human, Pair 16
Gene-Environment Interaction
Chromosomes, Human, Pair 17
5' Untranslated Regions
Environmental Exposure
Granuloma
Case-Control Studies
Inflammation

Keywords

  • 9/11
  • FDNY
  • firefighters
  • genetics
  • sarcoidosis
  • World Trade Center

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Health, Toxicology and Mutagenesis

Cite this

Genetic Variants Associated with FDNY WTC-Related Sarcoidosis. / Cleven, Krystal L.; Ye, Qian K.; Zeig-Owens, Rachel; Hena, Kerry M.; Montagna, Cristina; Shan, Jidong; Hosgood, Howard D.; Jaber, Nadia; Weiden, Michael D.; Colbeth, Hilary L.; Goldfarb, David G.; Spivack, Simon D.; Prezant, David J.

In: International journal of environmental research and public health, Vol. 16, No. 10, 23.05.2019.

Research output: Contribution to journalArticle

Cleven, Krystal L. ; Ye, Qian K. ; Zeig-Owens, Rachel ; Hena, Kerry M. ; Montagna, Cristina ; Shan, Jidong ; Hosgood, Howard D. ; 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. In: International journal of environmental research and public health. 2019 ; Vol. 16, No. 10.
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abstract = "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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AU - Cleven, Krystal L.

AU - Ye, Qian K.

AU - Zeig-Owens, Rachel

AU - Hena, Kerry M.

AU - Montagna, Cristina

AU - Shan, Jidong

AU - Hosgood, Howard D.

AU - Jaber, Nadia

AU - Weiden, Michael D.

AU - Colbeth, Hilary L.

AU - Goldfarb, David G.

AU - Spivack, Simon D.

AU - Prezant, David J.

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AB - 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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