Genetic variants in HLA genes are associated with diisocyanate-induced asthma in exposed workers

Details

• Personal Author:
  Bannerman-Thompson H ; Bernstein DI ; Cartier A ; Fluharty K ; Frye B ; Gautrin D ; Germolec DR ; Johnson VJ ; Lummus ZL ; Luster MI ; Malo J ; Marepalli R ; Wang W ; Yucesoy, Berran
• Description:
  Diisocyanates, low-molecular weight reactive chemicals extensively used in a variety of industrial processes, are one of the most common causes of occupational asthma. Both immunological and inflammatory mechanisms have been implicated in the development of diisocyanate-induced asthma (DA). A case-control study was conducted to investigate whether genetic variations in genes located within the major histocompatibility complex play a role in susceptibility to DA using a high density SNP map. The study population consisted of 140 workers exposed to diisocyanates (hexamethylene diisocyanate (HDI), methylene diphenyl diisocyanate, and toluene diisocyanate) of which 73 were diagnosed with DA based on a positive specific inhalation challenge and 67 were asymptomatic workers exposed to HDI. Genotype analysis was performed on genomic DNA, using Illumina GoldenGate Genotyping technology. The microarray platform consisted of 2,360 loci with an average spacing of 2 kb. After adjusting for potential confounders, single nucleotide polymorphisms in HLA-E (rs1573294), HLA-B (rs1811157), HLA-DOA (rs3128935), HLA-DQA2 (rs7773955), and HLA-DPB1 (rs928976) showed associations with altered risk of developing DA. Since HLA genes play a key role in the regulation of the immune response, variations in these genes may represent important disease modifiers that contribute to DA susceptibility. [Description provided by NIOSH]
• Subjects:
  Asthma Asthma, Occupational Case Reports Genetics Immune System Isocyanates Lung Nucleotides Occupational Exposure Occupational Health Respiratory System Respiratory Tract Diseases Safety

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• Keywords:
  Bronchial-asthma Case-studies Cyanates Employee-exposure Genes Genetic-factors Immune-reaction Lung-function Lung-irritants Nucleic-acids Pulmonary-function Respiratory-system-disorders

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• ISSN:
  1096-6080
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Abstract or Summary
• Place as Subject:
  California ; North Carolina ; Ohio ; OSHA Region 3 ; OSHA Region 4 ; OSHA Region 5 ; OSHA Region 9 ; 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:
  126
• NIOSHTIC Number:
  nn:20040568
• Citation:
  Toxicologist 2012 Mar; 126(Suppl 1):348
• CAS Registry Number:
  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:
  False
• Start Date:
  20060901
• Source Full Name:
  The Toxicologist. Society of Toxicology 51st Annual Meeting and ToxExpo, March 11-15, 2012, San Francisco, California
• Supplement:
  1
• End Date:
  20180831
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:2ee4ce273a5b9fae43a176f4766c4e8f1f18b1f4c398344a0457ca8ef867eb005cb3f4151583a14ca5074581a5b9dca81737562e96e8c4344802b077641a040c
• Download URL:
  https://stacks.cdc.gov/view/cdc/193372/cdc_193372_DS1.pdf
• File Type:
  [PDF - 463.88 KB ]