PMID- 31126090 OWN - NLM STAT- MEDLINE DCOM- 20191206 LR - 20200309 IS - 1660-4601 (Electronic) IS - 1661-7827 (Print) IS - 1660-4601 (Linking) VI - 16 IP - 10 DP - 2019 May 23 TI - Genetic Variants Associated with FDNY WTC-Related Sarcoidosis. LID - 10.3390/ijerph16101830 [doi] LID - 1830 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. FAU - Cleven, Krystal L AU - Cleven KL AD - Pulmonology Division, Department of Medicine, Montefiore Medical Center, Bronx, NY 10467, USA. kcleven@montefiore.org. AD - Pulmonology Division, Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10467, USA. kcleven@montefiore.org. FAU - Ye, Kenny AU - Ye K AUID- ORCID: 0000-0002-1466-855X AD - Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY 10461, USA. kenny.ye@einstein.yu.edu. FAU - Zeig-Owens, Rachel AU - Zeig-Owens R AD - Pulmonology Division, Department of Medicine, Montefiore Medical Center, Bronx, NY 10467, USA. rachel.zeig-owens@fdny.nyc.gov. AD - Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY 10461, USA. rachel.zeig-owens@fdny.nyc.gov. AD - Fire Department of the City of New York, Bureau of Health Services, Brooklyn, NY 11201, USA. rachel.zeig-owens@fdny.nyc.gov. FAU - Hena, Kerry M AU - Hena KM AD - Pulmonary & Critical Care Division, Department of Medicine, NYU School of Medicine, New York, NY 10016, USA. kerry.hena@nyulangone.org. FAU - Montagna, Cristina AU - Montagna C AUID- ORCID: 0000-0003-2343-5851 AD - Department of Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA. cristina.montagna@einstein.yu.edu. AD - Department of Pathology, Albert Einstein College of Medicine, Bronx, NY 10461, USA. cristina.montagna@einstein.yu.edu. AD - Molecular Cytogenetic Core, Albert Einstein College of Medicine, Bronx, NY 10461, USA. cristina.montagna@einstein.yu.edu. FAU - Shan, Jidong AU - Shan J AD - Department of Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA. jidong.shan@einstein.yu.edu. AD - Molecular Cytogenetic Core, Albert Einstein College of Medicine, Bronx, NY 10461, USA. jidong.shan@einstein.yu.edu. FAU - Hosgood, H Dean 3rd AU - Hosgood HD 3rd AD - Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY 10461, USA. dean.hosgood@einstein.yu.edu. FAU - Jaber, Nadia AU - Jaber N AD - Fire Department of the City of New York, Bureau of Health Services, Brooklyn, NY 11201, USA. nadia.jaber@fdny.nyc.gov. FAU - Weiden, Michael D AU - Weiden MD AD - Fire Department of the City of New York, Bureau of Health Services, Brooklyn, NY 11201, USA. michael.weiden@nyulangone.org. AD - Pulmonary & Critical Care Division, Department of Medicine, NYU School of Medicine, New York, NY 10016, USA. michael.weiden@nyulangone.org. FAU - Colbeth, Hilary L AU - Colbeth HL AD - Pulmonology Division, Department of Medicine, Montefiore Medical Center, Bronx, NY 10467, USA. hilary.colbeth@fdny.nyc.gov. AD - Fire Department of the City of New York, Bureau of Health Services, Brooklyn, NY 11201, USA. hilary.colbeth@fdny.nyc.gov. FAU - Goldfarb, David G AU - Goldfarb DG AD - Pulmonology Division, Department of Medicine, Montefiore Medical Center, Bronx, NY 10467, USA. david.goldfarb@fdny.nyc.gov. AD - Fire Department of the City of New York, Bureau of Health Services, Brooklyn, NY 11201, USA. david.goldfarb@fdny.nyc.gov. FAU - Spivack, Simon D AU - Spivack SD AD - Pulmonology Division, Department of Medicine, Montefiore Medical Center, Bronx, NY 10467, USA. simon.spivack@einstein.yu.edu. AD - Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY 10461, USA. simon.spivack@einstein.yu.edu. AD - Pulmonary & Critical Care Division, Department of Medicine, NYU School of Medicine, New York, NY 10016, USA. simon.spivack@einstein.yu.edu. AD - Department of Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA. simon.spivack@einstein.yu.edu. FAU - Prezant, David J AU - Prezant DJ AD - Pulmonology Division, Department of Medicine, Montefiore Medical Center, Bronx, NY 10467, USA. david.prezant@fdny.nyc.gov. AD - Fire Department of the City of New York, Bureau of Health Services, Brooklyn, NY 11201, USA. david.prezant@fdny.nyc.gov. AD - Pulmonary & Critical Care Division, Department of Medicine, NYU School of Medicine, New York, NY 10016, USA. david.prezant@fdny.nyc.gov. LA - eng GR - U01 OH011302/OH/NIOSH CDC HHS/United States GR - U01-OH010993/OH/NIOSH CDC HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. DEP - 20190523 PL - Switzerland TA - Int J Environ Res Public Health JT - International journal of environmental research and public health JID - 101238455 SB - IM MH - Adult MH - Case-Control Studies MH - Environmental Exposure/*adverse effects/statistics & numerical data MH - Female MH - Firefighters/statistics & numerical data MH - Humans MH - Male MH - New York City/epidemiology MH - Occupational Diseases/*epidemiology MH - Occupational Exposure/*adverse effects/statistics & numerical data MH - Sarcoidosis/*epidemiology/*genetics MH - *September 11 Terrorist Attacks PMC - PMC6572061 OTO - NOTNLM OT - 9/11 OT - FDNY OT - World Trade Center OT - firefighters OT - genetics OT - sarcoidosis COIS- The authors declare no conflict of interest. EDAT- 2019/05/28 06:00 MHDA- 2019/12/18 06:00 PMCR- 2019/05/01 CRDT- 2019/05/26 06:00 PHST- 2019/02/15 00:00 [received] PHST- 2019/05/02 00:00 [revised] PHST- 2019/05/19 00:00 [accepted] PHST- 2019/05/26 06:00 [entrez] PHST- 2019/05/28 06:00 [pubmed] PHST- 2019/12/18 06:00 [medline] PHST- 2019/05/01 00:00 [pmc-release] AID - ijerph16101830 [pii] AID - ijerph-16-01830 [pii] AID - 10.3390/ijerph16101830 [doi] PST - epublish SO - Int J Environ Res Public Health. 2019 May 23;16(10):1830. doi: 10.3390/ijerph16101830.