Haplotypes of IL-4 Receptor and CD14 Genetic Polymorphisms Are Markers of Susceptibility for Diisocyanate Asthma

Details

• Personal Author:
  Bernstein DI ; Boulet LP ; Cartier A ; Chakraborty R ; Cote J ; Hershey GK ; Tarlo S ; Wang N ; Wanner M
• Description:
  Diisocyanate asthma (DA) is associated with specific HLA-DQ alleles, glutathione-s-transferase and N-acetyltransferase genotypes. We evaluated polymorphisms for IL-4 receptor alpha (IL-4Rx), a common component of IL-4 and IL-13 receptors, IL-13, and CD14, a key constituent of the toll receptor complex. Studies were conducted in 18 workers with DA confirmed by inhalation challenge (DA+) and in 30 challenge negative (DA-) workers. Single nucleotide polymorphisms (snp) for IL-4Ralpha (Ile75Val, Glu400Ala, Glu 576 Arg or Q576R, Cys431Arg), IL-13 (R130Q) and CD14 (C159T) were analyzed to elucidate disease-associated genotypes. No associations were detected between DA and individual alleles. However, combinations of snps in the IL-4Ralpha and CD14 genes were found to be significantly associated with DA. The frequency of the IC haplotype (shared between I75V and C159T) was 0.44 in DA + workers vs. 023 among DA- subjects (p=0.04). The QC haplotype frequency (Q576R, C159T) of 0.667 in the DA + group was more frequent (0.425) than in the DA- groups (p=0.03). Furthermore, the frequency of IQC haplotype (l75V, Q576R, C159T) was 0.44 in DA + workers vs. 0.217 in the DA - group (p=0.04). The IC, QC and IQC haplotypes are significantly associated with the DA phenotype. Although the functional significance of these findings is uncertain, these haplotypes could be susceptibility markers for DA and may be useful aids in the diagnosis of DA. [Description provided by NIOSH]
• Subjects:
  Asthma Asthma, Occupational Occupational Health Respiratory Tract Diseases Safety
• Keywords:
  Bronchial-asthma Genotoxic-effects Humans Pulmonary-system-disorders Respiratory-system-disorders
• ISSN:
  1073-449X
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Abstract or Summary ; Proceedings
• Place as Subject:
  Ohio ; OSHA Region 5
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  167
• Issue:
  7
• NIOSHTIC Number:
  nn:20023070
• Citation:
  Am J Respir Crit Care Med 2003 Apr; 167(7):A580
• Federal Fiscal Year:
  2003
• NORA Priority Area:
  Disease and Injury: Asthma and Chronic Obstructive Pulmonary Disease
• Performing Organization:
  University of Cincinnati, Cincinnati, OH
• Peer Reviewed:
  False
• Start Date:
  19990930
• Source Full Name:
  American Journal of Respiratory and Critical Care Medicine, 2003 International Conference, The American Thoracic Society, Seattle, WA, May 16-21, 2003
• End Date:
  20030929
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:d1718aea82925f0a7d263484928e8471a2df6848fe787c5a904361b91e0a93d9fba439e5e204fbef72e8d6fb01823d9dc9da83bed0cf0d23e09d12ed85838920
• Download URL:
  https://stacks.cdc.gov/view/cdc/199654/cdc_199654_DS1.pdf
• File Type:
  [PDF - 271.03 KB ]