Interferon-gamma promoter is hypermethylated in blood DNA from workers with confirmed diisocyanate asthma

Details

• Personal Author:
  Bernstein DI ; Boulet LP ; Cartier A ; Gautrin D ; Ho SM ; Lummus ZL ; Ouyang B ; Ying J
• Description:
  Risk factors have not been identified that determine susceptibility for development of diisocyanate-induced occupational asthma (DA). We hypothesized that diisocyanate (DI) exposure could modify gene promoter regions regulating transcription of cytokine mediators and thereby influence expression of DA. A cross-sectional study was designed to investigate the promoter methylation status of candidate genes in DI-exposed workers. Subjects consisted of 131 workers in three groups: 40 cases with DA confirmed by a positive specific inhalation challenge (SIC) (DA+), 41 exposed workers with lower respiratory symptoms and negative SIC (DA-), and 50 asymptomatic exposed workers (AWs). We studied four candidate genes (GSTM1, DUSP22, IFN-y, and IL-4) for which altered promoter methylation has been previously investigated for relationships with a variety of other environmental exposures. Methylation status was determined using methylation-specific quantitative PCR performed on genomic DNA extracted from whole blood. Results showed that relative methylation of IFN-? promoter was significantly increased in DA+ in comparison with both comparator groups (DA- and AW), and it exhibited good sensitivity (77.5%) and specificity (80%) for identifying DA workers in a multivariate predictive model after adjusting for type of DI exposure, smoking status, methacholine PC20, and gender. IL-4 promoter was slightly less methylated only in DA+ compared with AW among nonsmoking workers. Both GSTM1 and DUSP22 promoter methylations were found not associated with DA. Our finding suggests that exposure to occupational chemicals could play a heretofore undefined mechanistic role via epigenetic modification of specific genes in the promoter region. [Description provided by NIOSH]
• Subjects:
  Blood Genetics Lung Men Occupational Health Respiratory System Respiratory Tract Diseases Risk Assessment Risk Factors Safety Women

  More +
• Keywords:
  Asthma Author Keywords: DNA Methylation Blood-cells Diisocyanate Environmental Exposure Exposure-levels Humans IFN-gamma Occupational Asthma Pulmonary-function Pulmonary-system Pulmonary-system-disorders Respiratory-system-disorders Risk-factors

  More +
• ISSN:
  1096-6080
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  Connecticut ; Ohio ; OSHA Region 1 ; OSHA Region 5
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  218-224
• Volume:
  133
• Issue:
  2
• NIOSHTIC Number:
  nn:20043533
• Citation:
  Toxicol Sci 2013 Jun; 133(2):218-224
• Contact Point Address:
  Shuk-Mei Ho, University of Cincinnati Medical Center, 3223 Eden Ave, Kettering Complex, Cincinnati, OH 45267-0056
• Email:
  shuk-mei.ho@uc.edu
• Federal Fiscal Year:
  2013
• Performing Organization:
  University of Cincinnati
• Peer Reviewed:
  True
• Start Date:
  20060901
• Source Full Name:
  Toxicological Sciences
• End Date:
  20180831
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:6bf18197707ecfe31d8ba9f285c376a0ca7b8851326894d898269ae88721dbdd8772516130949763b2e38c22f92e8856f02ec5e399e8d03decb5f9248c495a38
• Download URL:
  https://stacks.cdc.gov/view/cdc/195412/cdc_195412_DS1.pdf
• File Type:
  [PDF - 858.48 KB ]