Genetic variants in antioxidant genes are associated with diisocyanate-induced asthma

Details

• Personal Author:
  Bernstein DI ; Boulet L-P ; Cartier A ; Cruz M-J ; Fluharty K ; Gautrin D ; Germolec DR ; Johnson VJ ; Kissling GE ; Lummus ZL ; Luster MI ; Malo J-L ; Munoz X ; Quirce S ; Sastre J ; Tarlo SM ; Yucesoy, Berran
• Description:
  Diisocyanates are a common cause of occupational asthma, but risk factors are not well defined. A case-control study was conducted to investigate whether genetic variants of antioxidant defense genes, glutathione S-transferases (GSTM1, GSTT1, GSTM3, GSTP1), manganese superoxide dismutase (SOD2) and microsomal epoxide hydrolase (EPHX1) are associated with increased susceptibility to diisocyanate asthma (DA). The main study population consisted of 353 Caucasian French Canadians from among a larger sample of 410 diisocyanate-exposed workers in three groups: workers with specific inhalation challenge (SIC) confirmed DA (DA+, n=95); symptomatic diisocyanate workers with a negative SIC (DA-, n=116); and asymptomatic exposed workers (AW, n=142). Genotyping was performed on genomic DNA, using a 5' nuclease PCR assay. The SOD2 rs4880, GSTP1 rs1695 and EPHX1 rs2740171 variants were significantly associated with DA in both univariate and multivariate analyses. In the first logistic regression model comparing DA+ and DA- groups; SOD2 rs4880, GSTM1 (null), GSTP1 rs762803 and EPHX1 rs2854450 variants were associated with DA (p=0.004, p=0.047, p=0.021, p <0.001, respectively). Genotype combinations GSTT1*GSTP1 rs762803, GSTM1*EPHX1 rs2854450, EPHX1 rs2740168*EPHX1 rs1051741 and GSTP1 rs762803*EPHX1 rs2740168 were also associated with DA in this model (p=0.027, p=0.002, p=0.045, p=0.044, respectively). The GSTP1 rs1695, EPHX1 rs1051741 and rs2740171 variants showed an association with DA in the second model comparing DA+ and AW groups (p=0.040, p=0.019, p=0.002, respectively). The GSTM3 rs110913*EPHX1 rs1051741 genotype combination was also associated with DA under this model (p=0.042). The results suggest that variations in SOD2, GST, and EPHX1 genes and their interactions contribute to DA susceptibility. [Description provided by NIOSH]
• Subjects:
  Antioxidants Genetics Inhalation Exposure Lung Lung Diseases Occupational Health Respiratory System Respiratory Tract Diseases Safety
• Keywords:
  Antioxidant Author Keywords: Diisocyanates Exposure-levels Genes Genetics Inhalants Lung-burden Lung-disorders Lung-function Monomers Occupational Asthma Polymorphism Pulmonary-disorders Pulmonary-function Pulmonary-system Pulmonary-system-disorders Respiratory-system-disorders Single Nucleotide Sociological-factors Statistical-analysis

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• ISSN:
  1096-6080
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  North Carolina ; Ohio ; OSHA Region 3 ; OSHA Region 4 ; 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
• Pages in Document:
  166-173
• Volume:
  129
• Issue:
  1
• NIOSHTIC Number:
  nn:20041395
• Citation:
  Toxicol Sci 2012 Sep; 129(1):166-173
• Contact Point Address:
  Berran Yucesoy, PhD, National Institute for Occupational 39 Safety and 40 Health, Health Effects Laboratory Division, Toxicology and Molecular Biology Branch, 1095 41 Willowdale Road, M/S 3014, Morgantown, WV 26505
• Email:
  byucesoy@cdc.gov
• CAS Registry Number:
  Diphenylmethane diisocyanate (CAS RN 101-68-8) ; Hexamethylene diisocyanate (CAS RN 822-06-0) ; Toluene 2,4-diisocyanate (CAS RN 584-84-9)
• Federal Fiscal Year:
  2012
• 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:f4929211aab4e4a193db4cefc2167217d86687de5312774afe466244cc3d7f797f8701c8c126681f1363995e4ae61641673c2b4a2e765822e33aca12bad76d11
• Download URL:
  https://stacks.cdc.gov/view/cdc/193972/cdc_193972_DS1.pdf
• File Type:
  [PDF - 123.58 KB ]