Genetic variants in TNFa, TGFB1, PTGS1 and PTGS2 genes are associated with diisocyanate-induced asthma

Details

• Personal Author:
  Bernstein DI ; Boulet L-P ; Cartier A ; Cruz M-J ; Fluharty K ; Gautrin D ; Johnson VJ ; Kashon ML ; Lummus ZL ; Luster MI ; Munoz X ; Quirce S ; Sastre J ; Tarlo SM ; Yucesoy, Berran
• Description:
  Diisocyanates are the most common cause of occupational asthma, but risk factors are not well defined. A case-control study was conducted to investigate whether genetic variants in inflammatory response genes (TNFa, IL1a, IL1B, IL1RN, IL10, TGFB1, ADAM33, ALOX-5, PTGS1, PTGS2 and NAG-1/GDF15) are associated with increased susceptibility to diisocyanate asthma (DA). These genes were selected based on their role in asthmatic inflammatory processes and previously reported associations with asthma phenotypes. The main study population consisted of 237 Caucasian French Canadians from among a larger sample of 280 diisocyanate-exposed workers in two groups: workers with specific inhalation challenge (SIC) confirmed DA (DA+, n=95) and asymptomatic exposed workers (AW, n=142). Genotyping was performed on genomic DNA, using a 50 nuclease PCR assay. After adjusting for potentially confounding variables of age, smoking status and duration of exposure, the PTGS1 rs5788 and TGFB1 rs1800469 single nucleotide polymorphisms (SNP) showed a protective effect under a dominant model (OR=0.38; 95% CI=0.17, 0.89 and OR=0.38; 95% CI=0.18, 0.74, respectively) while the TNFa rs1800629 SNP was associated with an increased risk of DA (OR=2.08; 95% CI=1.03, 4.17). Additionally, the PTGS2 rs20417 variant showed an association with increased risk of DA in a recessive genetic model (OR=6.40; 95% CI=1.06, 38.75). These results suggest that genetic variations in TNFa, TGFB1, PTGS1 and PTGS2 genes contribute to DA susceptibility. [Description provided by NIOSH]
• Subjects:
  Asthma Asthma, Occupational Chemistry Genetics Lung Occupational Health Respiratory System Respiratory Tract Diseases Risk Assessment Risk Factors Safety Workplace

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• Keywords:
  Author Keywords: Cytokine Bronchial-asthma Chemical-composition Chemical-properties Diisocyanates Exposure-levels Inflammation Occupational Asthma Proteins Pulmonary-function Pulmonary-system Pulmonary-system-disorders Respiration Respiratory-system-disorders Risk-factors Single Nucleotide Polymorphism SNP Work-environment Workers

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• ISSN:
  1547-691X
• 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:
  119-126
• Volume:
  13
• Issue:
  1
• NIOSHTIC Number:
  nn:20046169
• Citation:
  J Immunotoxicol 2016 Jan; 13(1):119-126
• Contact Point Address:
  Dr. Berran Yucesoy, Division of Immunology, Allergy and Rheumatology, University of Cincinnati, College of Medicine, Cincinnati, OH
• Email:
  berranyucesoy@gmail.com
• Federal Fiscal Year:
  2016
• NORA Priority Area:
  Healthcare and Social Assistance ; Services ; Construction ; Manufacturing
• Performing Organization:
  University of Cincinnati
• Peer Reviewed:
  True
• Start Date:
  20060901
• Source Full Name:
  Journal of Immunotoxicology
• End Date:
  20180831
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:92372babaf70dcc0a5ed825b190c76fe526a57fa3a744226d53823eafe6c1d31f70b52e8f97429a1d289437c349544b800cc24da44f0fbfb1f8312a9de03d428
• Download URL:
  https://stacks.cdc.gov/view/cdc/201300/cdc_201300_DS1.pdf
• File Type:
  [PDF - 503.90 KB ]