{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T22:58:02Z","timestamp":1785538682299,"version":"3.56.0"},"reference-count":32,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2019,5,23]],"date-time":"2019-05-23T00:00:00Z","timestamp":1558569600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000125","name":"National Institute for Occupational Safety and Health","doi-asserted-by":"publisher","award":["U01-OH010993"],"award-info":[{"award-number":["U01-OH010993"]}],"id":[{"id":"10.13039\/100000125","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJERPH"],"abstract":"<jats:p>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\u2019 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.<\/jats:p>","DOI":"10.3390\/ijerph16101830","type":"journal-article","created":{"date-parts":[[2019,5,24]],"date-time":"2019-05-24T02:22:00Z","timestamp":1558664520000},"page":"1830","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Genetic Variants Associated with FDNY WTC-Related Sarcoidosis"],"prefix":"10.3390","volume":"16","author":[{"given":"Krystal L.","family":"Cleven","sequence":"first","affiliation":[{"name":"Pulmonology Division, Department of Medicine, Montefiore Medical Center, Bronx, NY 10467, USA"},{"name":"Pulmonology Division, Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10467, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1466-855X","authenticated-orcid":false,"given":"Kenny","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY 10461, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Zeig-Owens","sequence":"additional","affiliation":[{"name":"Pulmonology Division, Department of Medicine, Montefiore Medical Center, Bronx, NY 10467, USA"},{"name":"Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY 10461, USA"},{"name":"Fire Department of the City of New York, Bureau of Health Services, Brooklyn, NY 11201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerry M.","family":"Hena","sequence":"additional","affiliation":[{"name":"Pulmonary &amp; Critical Care Division, Department of Medicine, NYU School of Medicine, New York, NY 10016, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2343-5851","authenticated-orcid":false,"given":"Cristina","family":"Montagna","sequence":"additional","affiliation":[{"name":"Department of Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA"},{"name":"Department of Pathology, Albert Einstein College of Medicine, Bronx, NY 10461, USA"},{"name":"Molecular Cytogenetic Core, Albert Einstein College of Medicine, Bronx, NY 10461, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jidong","family":"Shan","sequence":"additional","affiliation":[{"name":"Department of Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA"},{"name":"Molecular Cytogenetic Core, Albert Einstein College of Medicine, Bronx, NY 10461, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"III","given":"H. Dean","family":"Hosgood","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY 10461, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadia","family":"Jaber","sequence":"additional","affiliation":[{"name":"Fire Department of the City of New York, Bureau of Health Services, Brooklyn, NY 11201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael D.","family":"Weiden","sequence":"additional","affiliation":[{"name":"Fire Department of the City of New York, Bureau of Health Services, Brooklyn, NY 11201, USA"},{"name":"Pulmonary &amp; Critical Care Division, Department of Medicine, NYU School of Medicine, New York, NY 10016, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hilary L.","family":"Colbeth","sequence":"additional","affiliation":[{"name":"Pulmonology Division, Department of Medicine, Montefiore Medical Center, Bronx, NY 10467, USA"},{"name":"Fire Department of the City of New York, Bureau of Health Services, Brooklyn, NY 11201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David G.","family":"Goldfarb","sequence":"additional","affiliation":[{"name":"Pulmonology Division, Department of Medicine, Montefiore Medical Center, Bronx, NY 10467, USA"},{"name":"Fire Department of the City of New York, Bureau of Health Services, Brooklyn, NY 11201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon D.","family":"Spivack","sequence":"additional","affiliation":[{"name":"Pulmonology Division, Department of Medicine, Montefiore Medical Center, Bronx, NY 10467, USA"},{"name":"Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY 10461, USA"},{"name":"Pulmonary &amp; Critical Care Division, Department of Medicine, NYU School of Medicine, New York, NY 10016, USA"},{"name":"Department of Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Prezant","sequence":"additional","affiliation":[{"name":"Pulmonology Division, Department of Medicine, Montefiore Medical Center, Bronx, NY 10467, USA"},{"name":"Fire Department of the City of New York, Bureau of Health Services, Brooklyn, NY 11201, USA"},{"name":"Pulmonary &amp; Critical Care Division, Department of Medicine, NYU School of Medicine, New York, NY 10016, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,5,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1885","DOI":"10.1164\/ajrccm.164.10.2104046","article-title":"Clinical characteristics of patients in a case control study of sarcoidosis","volume":"164","author":"Baughman","year":"2001","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.mayocp.2015.10.024","article-title":"Epidemiology of Sarcoidosis 1946\u20132013: A Population-Based Study","volume":"91","author":"Ungprasert","year":"2016","journal-title":"Mayo Clin. Proc."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.1378\/chest.116.5.1183","article-title":"The incidence, prevalence, and severity of sarcoidosis in New York City firefighters","volume":"116","author":"Prezant","year":"1999","journal-title":"Chest"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1016\/j.rmed.2017.06.004","article-title":"Post-9\/11 sarcoidosis in WTC-exposed firefighters and emergency medical service workers","volume":"132","author":"Webber","year":"2017","journal-title":"Respir. Med."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Rossides, M., Grunewald, J., Eklund, A., Kullberg, S., Di Giuseppe, D., Askling, J., and Arkema, E.V. (2018). Familial aggregation and heritability of sarcoidosis: A Swedish nested case-control study. Eur. Respir. J., 52.","DOI":"10.1183\/13993003.00385-2018"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2085","DOI":"10.1164\/ajrccm.164.11.2106001","article-title":"Familial aggregation of sarcoidosis. A case-control etiologic study of sarcoidosis (ACCESS)","volume":"164","author":"Rybicki","year":"2001","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1086\/378097","article-title":"HLA-DRB1*1101: A significant risk factor for sarcoidosis in blacks and whites","volume":"73","author":"Rossman","year":"2003","journal-title":"Am. J. Hum. Genet."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"826","DOI":"10.1016\/j.humimm.2005.04.003","article-title":"Severe pulmonary sarcoidosis is strongly associated with the haplotype HLA-DQB1*0602-DRB1*150101","volume":"66","author":"Voorter","year":"2005","journal-title":"Hum. Immunol."},{"key":"ref_9","first-page":"143","article-title":"TNF-alpha and HLA-DR genotyping as potential prognostic markers in pulmonary sarcoidosis","volume":"10","author":"Swider","year":"1999","journal-title":"Eur. Cytokine Netw."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1165\/rcmb.2014-0227OC","article-title":"Association of HLA-DRB1 with Sarcoidosis Susceptibility and Progression in African Americans","volume":"53","author":"Levin","year":"2015","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1164\/rccm.200512-1839OC","article-title":"Functional prostaglandin-endoperoxide synthase 2 polymorphism predicts poor outcome in sarcoidosis","volume":"174","author":"Hill","year":"2006","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e43907","DOI":"10.1371\/journal.pone.0043907","article-title":"Genome-wide association study of African and European Americans implicates multiple shared and ethnic specific loci in sarcoidosis susceptibility","volume":"7","author":"Adrianto","year":"2012","journal-title":"PLoS ONE"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1183\/09031936.00010209","article-title":"CARD15\/NOD2 polymorphisms are associated with severe pulmonary sarcoidosis","volume":"35","author":"Sato","year":"2010","journal-title":"Eur. Respir. J."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1038\/ng1519","article-title":"Sarcoidosis is associated with a truncating splice site mutation in BTNL2","volume":"37","author":"Valentonyte","year":"2005","journal-title":"Nat. Genet."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1086\/444435","article-title":"The BTNL2 gene and sarcoidosis susceptibility in African Americans and Whites","volume":"77","author":"Rybicki","year":"2005","journal-title":"Am. J. Hum. Genet."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/j.chest.2017.10.014","article-title":"Clinical Course of Sarcoidosis in World Trade Center-Exposed Firefighters","volume":"153","author":"Hena","year":"2018","journal-title":"Chest"},{"key":"ref_17","first-page":"19","article-title":"The WASOG Sarcoidosis Organ Assessment Instrument: An update of a previous clinical tool","volume":"31","author":"Judson","year":"2014","journal-title":"Sarcoidosis Vasc. Diffus. Lung Dis. Off. J. WASOG"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1056\/NEJMoa021300","article-title":"Cough and bronchial responsiveness in firefighters at the World Trade Center site","volume":"347","author":"Prezant","year":"2002","journal-title":"New Engl. J. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"102033","DOI":"10.18632\/oncotarget.22116","article-title":"Development and validation of a targeted next generation DNA sequencing panel outperforming whole exome sequencing for the identification of clinically relevant genetic variants","volume":"8","author":"Miller","year":"2017","journal-title":"Oncotarget"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e0133742","DOI":"10.1371\/journal.pone.0133742","article-title":"Development of a Targeted Multi-Disorder High-Throughput Sequencing Assay for the Effective Identification of Disease-Causing Variants","volume":"10","author":"Delio","year":"2015","journal-title":"PLoS ONE"},{"key":"ref_21","first-page":"271","article-title":"Primary Hepatic Small Cell Carcinoma: Two Case Reports, Molecular Characterization and Pooled Analysis of Known Clinical Data","volume":"36","author":"Shastri","year":"2016","journal-title":"Anticancer Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1002\/mgg3.323","article-title":"Compound heterozygous CASQ2 mutations and long-term course of catecholaminergic polymorphic ventricular tachycardia","volume":"5","author":"Josephs","year":"2017","journal-title":"Mol. Genet. Genom. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1414","DOI":"10.1378\/chest.06-2114","article-title":"World Trade Center \u201csarcoid-like\u201d granulomatous pulmonary disease in New York City Fire Department rescue workers","volume":"131","author":"Izbicki","year":"2007","journal-title":"Chest"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1002\/ajim.20924","article-title":"\u201cSarcoid like\u201d granulomatous pulmonary disease in World Trade Center disaster responders","volume":"54","author":"Crowley","year":"2011","journal-title":"Am. J. Ind. Med."},{"key":"ref_25","first-page":"A1740","article-title":"Characteristics of sarcoidosis in residents and workers exposed to World Trade Center (WTC) dust, gas and fumes presenting for medical care","volume":"181","author":"Parsia","year":"2010","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1097\/JOM.0b013e31822a3596","article-title":"Sarcoidosis diagnosed after September 11, 2001, among adults exposed to the World Trade Center disaster","volume":"53","author":"Jordan","year":"2011","journal-title":"J. Occup. Environ. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"53","DOI":"10.3109\/10428194.2010.532888","article-title":"Association of HLA-DQB1 alleles with risk of follicular lymphoma","volume":"52","author":"Akers","year":"2011","journal-title":"Leuk. Lymphoma"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1034\/j.1399-0039.2000.560107.x","article-title":"HLA-DQB1*0601 is primarily associated with the susceptibility to cardiac sarcoidosis","volume":"56","author":"Naruse","year":"2000","journal-title":"Tissue Antigens"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1016\/j.atherosclerosis.2008.07.018","article-title":"Association of polymorphisms in cyclooxygenase (COX)-2 with coronary and carotid calcium in the Diabetes Heart Study","volume":"203","author":"Rudock","year":"2009","journal-title":"Atherosclerosis"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2221","DOI":"10.1001\/jama.291.18.2221","article-title":"A polymorphism in the cyclooxygenase 2 gene as an inherited protective factor against myocardial infarction and stroke","volume":"291","author":"Cipollone","year":"2004","journal-title":"JAMA"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/j.jaci.2004.05.030","article-title":"Functional effects and gender association of COX-2 gene polymorphism G-765C in bronchial asthma","volume":"114","author":"Szczeklik","year":"2004","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"7146","DOI":"10.1038\/ncomms8146","article-title":"Major histocompatibility complex associations of ankylosing spondylitis are complex and involve further epistasis with ERAP1","volume":"6","author":"Cortes","year":"2015","journal-title":"Nat. Commun."}],"container-title":["International Journal of Environmental Research and Public Health"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-4601\/16\/10\/1830\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T12:54:34Z","timestamp":1760187274000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-4601\/16\/10\/1830"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,5,23]]},"references-count":32,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2019,5]]}},"alternative-id":["ijerph16101830"],"URL":"https:\/\/doi.org\/10.3390\/ijerph16101830","relation":{},"ISSN":["1660-4601"],"issn-type":[{"value":"1660-4601","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,5,23]]}}}