Interferon Gamma Promoter Is Hypermethylated in Blood DNA from Workers with Confirmed Diisocyanate Asthma

Details

• Personal Author:
  Bernstein D ; Boulet LP ; Cartier A ; Cruz M ; Gautrin D ; Ho SM ; Lummus ZL ; Munoz X ; Ouyang B ; Quirce S ; Sastre J ; Tarlo SM ; Ying J
• Description:
  Objectives: Diisocyanates (DIs) are leading causes of occupational asthma. Investigators are still unable to identify or define risk factors that determine susceptibility for development of DI-induced occupational asthma. Occupational chemical exposures could modify promoter regions regulating transcription of cytokine mediators or protective proteins and thereby influence expression of DA. To test this hypothesis, we performed a case control study of DI exposed workers with and without confirmed DA, investigating DNA methylation status of candidate gene promoter regions. Methods: 131 subjects were studied including: 40 workers with DA (DA+) confirmed by a positive specific inhalation challenge (SIC); 41 exposed workers with lower respiratory symptoms and negative SICs (DA-); and 50 asymptomatic exposed workers (AWs). 10-11 subjects from each aforementioned group were current smokers and the rest never smokers. DNA was extracted from blood and bisulfite-converted for analysis of methylation status of gene promoters using methylation-specific-quantitative PCR. Results: Promoter methylation status was measured for GSPM1, DUSP22, IFN-, and IL-4 genes. GSPM1and DUSP22 showed no statistically difference in degree of promoter methylation among the three study groups. Non-smoking subjects in DA+ showed 4-7% less-methylation of IL-4 promoter compared to DA- and AW. Interestingly, smoking subjects showed about 14% increased IL-4 promoter methylation in DA+ compared to DA- and AW. The IFN- promoter, however, was found to be hypermethylated in DA+ (median 68.1% methylation) compared to DA- (median 37% methylation) and AW (median 31.7% methylation). The degree of methylation was statistically different among the subjects (p=0.001 in DA+ vs. DA-, p=0.002 in DA+ vs. AW). There was no difference in the degree of IFN- promoter methylation between DA- and AW (p=0.70). Univariate model had modest accuracy of IFN methylation in identifying DA+ workers at 60% sensitivity and 81.3% specificity. Multivariate models through adjusting covariate predictors (exposure, smoking status, PC20 and gender) exhibited improved sensitivity (77.5%) and specificity (80%). Conclusion: DA+ was highly associated with IFN- promoter hypermethylation. Methylation status of IFN promoter, combining with multivariate model can differentiate DA from non-DA workers with relative high sensitivity and specificity. [Description provided by NIOSH]
• Subjects:
  Asthma, Occupational Biomarkers Isocyanates Occupational Exposure Occupational Health Respiratory System Respiratory Tract Diseases Safety
• Keywords:
  Cytokines Diisocyanates Genetic Factors Occupational Asthma Occupational Exposure Respiratory Diseases
• Publisher:
  Work Wellness and Disability Prevention Institute (WWDPI)
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Abstract or Summary
• Place as Subject:
  Maryland ; Ohio ; OSHA Region 3 ; OSHA Region 5
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  68
• NIOSHTIC Number:
  nn:20054288
• Citation:
  Isocyanates & Health: Past, Present and Future, April 3-4, 2013, Potomac, Maryland. Vancouver, BC, Canada: Work Wellness and Disability Prevention Institute (WWDPI), 2013 Apr; :68
• Email:
  bernstdd@ucmail.uc.edu
• Federal Fiscal Year:
  2013
• Performing Organization:
  University of Cincinnati
• Peer Reviewed:
  False
• Start Date:
  20060901
• Source Full Name:
  Isocyanates & Health: Past, Present and Future, April 3-4, 2013, Potomac, Maryland
• End Date:
  20180831
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:26b2ac754ba4410e924dab16cb4e762953c52359de51c89016b3d40761a4b24a6e39b9841ed3f2246893f77a4d7147f90407458f3f686f062f91867ecdde1d26
• Download URL:
  https://stacks.cdc.gov/view/cdc/216882/cdc_216882_DS1.pdf
• File Type:
  [PDF - 703.32 KB ]