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Int J Environ Res Public Health. 2019 May 23;16(10). pii: E1830. doi: 10.3390/ijerph16101830.

Genetic Variants Associated with FDNY WTC-Related Sarcoidosis.

Cleven KL1,2, Ye K3, Zeig-Owens R4,5,6, Hena KM7, Montagna C8,9,10, Shan J11,12, Hosgood HD 3rd13, Jaber N14, Weiden MD15,16, Colbeth HL17,18, Goldfarb DG19,20, Spivack SD21,22,23,24, Prezant DJ25,26,27.

Author information

1
Pulmonology Division, Department of Medicine, Montefiore Medical Center, Bronx, NY 10467, USA. kcleven@montefiore.org.
2
Pulmonology Division, Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10467, USA. kcleven@montefiore.org.
3
Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY 10461, USA. kenny.ye@einstein.yu.edu.
4
Pulmonology Division, Department of Medicine, Montefiore Medical Center, Bronx, NY 10467, USA. rachel.zeig-owens@fdny.nyc.gov.
5
Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY 10461, USA. rachel.zeig-owens@fdny.nyc.gov.
6
Fire Department of the City of New York, Bureau of Health Services, Brooklyn, NY 11201, USA. rachel.zeig-owens@fdny.nyc.gov.
7
Pulmonary & Critical Care Division, Department of Medicine, NYU School of Medicine, New York, NY 10016, USA. kerry.hena@nyulangone.org.
8
Department of Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA. cristina.montagna@einstein.yu.edu.
9
Department of Pathology, Albert Einstein College of Medicine, Bronx, NY 10461, USA. cristina.montagna@einstein.yu.edu.
10
Molecular Cytogenetic Core, Albert Einstein College of Medicine, Bronx, NY 10461, USA. cristina.montagna@einstein.yu.edu.
11
Department of Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA. jidong.shan@einstein.yu.edu.
12
Molecular Cytogenetic Core, Albert Einstein College of Medicine, Bronx, NY 10461, USA. jidong.shan@einstein.yu.edu.
13
Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY 10461, USA. dean.hosgood@einstein.yu.edu.
14
Fire Department of the City of New York, Bureau of Health Services, Brooklyn, NY 11201, USA. nadia.jaber@fdny.nyc.gov.
15
Fire Department of the City of New York, Bureau of Health Services, Brooklyn, NY 11201, USA. michael.weiden@nyulangone.org.
16
Pulmonary & Critical Care Division, Department of Medicine, NYU School of Medicine, New York, NY 10016, USA. michael.weiden@nyulangone.org.
17
Pulmonology Division, Department of Medicine, Montefiore Medical Center, Bronx, NY 10467, USA. hilary.colbeth@fdny.nyc.gov.
18
Fire Department of the City of New York, Bureau of Health Services, Brooklyn, NY 11201, USA. hilary.colbeth@fdny.nyc.gov.
19
Pulmonology Division, Department of Medicine, Montefiore Medical Center, Bronx, NY 10467, USA. david.goldfarb@fdny.nyc.gov.
20
Fire Department of the City of New York, Bureau of Health Services, Brooklyn, NY 11201, USA. david.goldfarb@fdny.nyc.gov.
21
Pulmonology Division, Department of Medicine, Montefiore Medical Center, Bronx, NY 10467, USA. simon.spivack@einstein.yu.edu.
22
Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY 10461, USA. simon.spivack@einstein.yu.edu.
23
Pulmonary & Critical Care Division, Department of Medicine, NYU School of Medicine, New York, NY 10016, USA. simon.spivack@einstein.yu.edu.
24
Department of Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA. simon.spivack@einstein.yu.edu.
25
Pulmonology Division, Department of Medicine, Montefiore Medical Center, Bronx, NY 10467, USA. david.prezant@fdny.nyc.gov.
26
Fire Department of the City of New York, Bureau of Health Services, Brooklyn, NY 11201, USA. david.prezant@fdny.nyc.gov.
27
Pulmonary & Critical Care Division, Department of Medicine, NYU School of Medicine, New York, NY 10016, USA. david.prezant@fdny.nyc.gov.

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.

KEYWORDS:

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

PMID:
31126090
DOI:
10.3390/ijerph16101830
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