Association of genetic variations in antioxidant enzyme genes with diisocyanate-induced asthma in exposed workers

Details

• Personal Author:
  Bernstein DI ; Fluharty K ; Germolec DR ; Johnson VJ ; Kissling GE ; Lummus ZL ; Luster MI ; Slaven, James E. ; Yucesoy, Berran
• Description:
  Diisocyanates are the most common cause of occupational asthma induced by low molecular- weight agents. It has been shown that diisocyanates induce oxidative stress when they react with specific proteins in human airway epithelial cells and this process contributes to the pathogenesis of diisocyanate-induced asthma (DA). In this respect, variability in the antioxidant defenses may play a role in DA susceptibility. A case-control study was conducted to investigate whether genetic variations within antioxidant enzyme genes, glutathione S-transferases (GSTM1- GSTT1, GSTM3, GSTP1), manganese superoxide dismutase (MnSOD) and microsomal epoxide hydrolase (EPHX1), play a role in susceptibility to DA. The study population consisted of 252 workers exposed to diisocyanates (hexamethylene diisocyanate, methylene diphenyl diisocyanate, and toluene diisocyanate) of which 102 were diagnosed with DA based on a positive specific inhalation challenge. Genotype analysis was performed on genomic DNA, using a 5' nuclease PCR assay. The EPHX1 SNP (rs2740171) and GSTT1 gene deletion were associated with altered risk of developing DA after adjusting for potential confounders. Since EPHX1 and GSTT1 genes are important components of lung defense against oxidative stress, variations in these genes which regulate their expression may represent important disease modifiers and contribute to DA susceptibility. [Description provided by NIOSH]
• Subjects:
  Genetics Hypersensitivity Irritants Lung Occupational Health Oxidants Respiratory Hypersensitivity Respiratory System Risk Assessment Risk Factors Safety

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• Keywords:
  Allergic-reactions Allergies Biological-effects Genetic-factors Inhalation-studies Lung-function Lung-irritants Molecular-biology Molecular-structure Oxidative-metabolism Oxidative-processes Physiological-effects Pulmonary-function Pulmonary-system Quantitative-analysis Respiratory-hypersensitivity Respiratory-irritants Risk-analysis Risk-factors Statistical-analysis Tissue-disorders

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• ISSN:
  1096-6080
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Abstract or Summary
• Place as Subject:
  District of Columbia ; Ohio ; OSHA Region 3 ; OSHA Region 5 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  120
• NIOSHTIC Number:
  nn:20038513
• Citation:
  Toxicologist 2011 Mar; 120(Suppl 2):293
• Federal Fiscal Year:
  2011
• NORA Priority Area:
  Healthcare and Social Assistance ; Services
• Performing Organization:
  University of Cincinnati
• Peer Reviewed:
  False
• Start Date:
  20060901
• Source Full Name:
  The Toxicologist. Society of Toxicology 50th Annual Meeting and ToxExpo, March 6-10, 2011, Washington, DC
• Supplement:
  2
• End Date:
  20180831
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:9dd25c824c30feb7b870043971452c8a7e839a5ac8e09ff04614ee40c1233762c4f03a5be706be481678cff6a01dcc78389c76fd692c031a41fbd4cb51923a19
• Download URL:
  https://stacks.cdc.gov/view/cdc/192199/cdc_192199_DS1.pdf
• File Type:
  [PDF - 1.09 MB ]