Dataset Information

Genetic Variants Associated with FDNY WTC-Related Sarcoidosis.

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.

SUBMITTER: Cleven KL

PROVIDER: S-EPMC6572061 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Genetic Variants Associated with FDNY WTC-Related Sarcoidosis.

Cleven Krystal L KL Ye Kenny K Zeig-Owens Rachel R Hena Kerry M KM Montagna Cristina C Shan Jidong J Hosgood H Dean HD Jaber Nadia N Weiden Michael D MD Colbeth Hilary L HL Goldfarb David G DG Spivack Simon D SD Prezant David J DJ

International journal of environmental research and public health 20190523 10

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 sarcoid ...[more]

PMID: 31126090

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Project description:AimLarge interindividual variability in morphine pharmacokinetics (PK) could contribute to variability in morphine analgesia and adverse events. Respiratory depression (RD) and postoperative nausea and vomiting (PONV) are significant adverse drug response of intravenous morphine in the perioperative setting limiting its efficacy in achieving adequate surgical pain relief. OCT1 is a transporter in the liver that transports morphine from the bloodstream into hepatocytes. Earlier we reported association of genetic polymorphisms in OCT1 with morphine PK, and lower morphine clearance in Caucasian children as compared with African-American (AA) children. The aim of this study is to identify the association between common OCT1 genotypes affecting morphine's PK and clinically important postoperative morphine-related adverse outcomes.MethodsAfter obtaining institutional review board (IRB) approval and informed consents, 311 children ages 6-15 years, American Society of Anesthesiologists' physical status 1 or 2 scheduled for tonsillectomy who received standard anesthetic, surgical and postoperative care were recruited. Clinical data collected included postoperative pain scores, total opioid use, incidence of PONV and RD. Four nonsynonymous SNPs of the OCT1 gene (rs12208357, rs34130495, rs72552763 and rs34059508) in each patient were genotyped using commercially available TaqMan assays. We investigated the genetic association of OCT1 with incidences of postoperative RD and PONV.ResultsCaucasian and AA children differed significantly in the incidence of obstructive sleep apnea (p < 0.001) and total morphine use (p = 0.028). There were incidences of prolonged post anesthesia care unit stay in 7% of Caucasian children, while no such incidences were observed for AA children (p = 0.05). OCT1 polymorphism rs12208357 was associated with high incidences of PONV and PONV leading to prolonged post anesthesia care unit stay (p < 0.05). A significant association was also found between rs72552763 GAT deletion and high incidence of RD (p = 0.007).ConclusionChildren with certain OCT1 genotypes are associated with higher risk for RD and PONV following morphine administration leading to prolonged hospital stay. The OCT1 transporters' effects on morphine's PK could explain this association.

Dataset Information

Genetic Variants Associated with FDNY WTC-Related Sarcoidosis.

Publications

Genetic Variants Associated with FDNY WTC-Related Sarcoidosis.

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