Novel Gene-Environment Associations with Diisocyanate Induced Asthma

Details

• Personal Author:
  Bernstein DI ; Boulet L ; Cartier A ; Gautrin D ; Hershey GK ; Kissling G ; Langmeyer S ; Lummus ZL ; Luster M ; Malo J ; Rao M ; Sastre J ; Tarlo S ; Yucesoy, Berran
• Description:
  Rationale: Risk and susceptibility factors for Diisocyanate Asthma (DA) are poorly defined. We used candidate gene approaches to define genetic susceptibility for DA in workers exposed to hexamethylene-(HDI), methylene diphenyl-(MDI) or toluene-(TDI) diisocyanate. Methods: DNA was collected from HDI, MDI or TDI exposed symptomatic workers with: DA (n=103) confirmed by specific inhalation challenge (SIC); non-DA defined by negative SIC (n=115). Asymptomatic HDI exposed workers (CTRL) (n=150) were also studied. Genotyping was performed with the following SNPs: IL-4 receptor alpha (IL4RA) (I75V, E400A, Q576R); IL-13 (R130Q); CD14 (C159T); glutathione transferases (GSTP1/Ile-Val, GSTT1/deletion, GSTM1); superoxide dismutase2 (MnSOD/A-V); epoxide hydrolase (EPHX Exon3, EPHX Exon4). DNA microarray was used to assess associations with 52 candidate asthma genes (772 SNPs) using a gene centric analytic approach. Results: Among HDI workers, workers with DA were more likely to have IL4RA II/CD14 CT (OR=3.1; 95%CI: 1.3, 7.3) and IL4RA II/IL13RR/CD14CT (OR=4; 95% CI: 1.4, 11.6) combined genotypes versus non-DA workers. The same combined genotypes were significantly associated with DA when compared with HDI CTRL workers. The MnSOD/VV genotype was individually associated with DA (p<0.05). Microarray data using gene centric analysis revealed three genes associated with DA: hydroxyacid oxidase/HAO1 (p= .01), plasminogen activator inhibitor 1/SERPIN1 (p= .05), and serine peptidase inhibitor B3/SERPINB3 (p=.05). Conclusions: Genotype combinations of SNPs associated with Th2 cytokines, anti-oxidant enzymes (MnSOD, HAO1), the innate immune response (CD14), airway remodeling (SERPIN1, SERPINB3), and HDI exposure may define susceptibility to DA. [Description provided by NIOSH]
• Subjects:
  Asthma Asthma, Occupational Genetics Occupational Health Respiratory Tract Diseases Safety
• Keywords:
  Bronchial-asthma Gene-mutation Genes Pulmonary-system-disorders Respiratory-system-disorders
• ISSN:
  0091-6749
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  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:
  125
• Issue:
  2
• NIOSHTIC Number:
  nn:20036591
• Citation:
  J Allergy Clin Immunol 2010 Feb; 125(2)(S1):AB357-AB358
• CAS Registry Number:
  Cyclohexane (CAS RN 110-82-7) ; Diphenylmethane diisocyanate (CAS RN 101-68-8) ; Toluene 2,4-diisocyanate (CAS RN 584-84-9)
• Federal Fiscal Year:
  2010
• NORA Priority Area:
  Healthcare and Social Assistance ; Services
• Peer Reviewed:
  False
• Source Full Name:
  Journal of Allergy and Clinical Immunology. 2010 American Academy of Allergy, Asthma & Immunology (AAAAI) Annual Meeting New Orleans, Louisiana, February 26-March 2, 2010
• Supplement:
  1
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:abd537a4dfb6a11185dbedd46c424d8fa9d43d2c2b240ef8c4eef3cbbf9c7b8dbbf20603452c91edde4a0ec78ee0245b44e35e1f582f23483e5e10f0f154b3c4
• Download URL:
  https://stacks.cdc.gov/view/cdc/187954/cdc_187954_DS1.pdf
• File Type:
  [PDF - 59.16 KB ]