CTNNA3 (alpha-catenin) gene variants are associated with diisocyanate asthma: a replication study in a Caucasian worker population

Details

• Personal Author:
  Bernstein DI ; Boulet L-P ; Cartier A ; Cruz M-J ; Fluharty K ; Gautrin D ; Germolec D ; Johnson VJ ; Kashon M ; Lummus ZL ; Luster MI ; Malo J-L ; Munoz X ; Quirce S ; Sastre J ; Tarlo SM ; Yucesoy, Berran
• Description:
  Recently, a genome-wide association study (GWAS) conducted in Korean subjects identified four CTNNA3 (alpha-T catenin) single nucleotide polymorphisms (SNPs) (rs10762058, rs7088181, rs1786929, and rs4378283) associated with diisocyanate-induced occupational asthma (DA). The CTNNA3 gene codes for a cadherin involved in formation of stretch-resistant cell-cell adhesions. We conducted a candidate gene association study to replicate these findings in Caucasian workers. Genotyping was performed on DNA using a 5L nuclease PCR assay collected from 410 diisocyanate exposed and predominantly Canadian workers including 132 workers with DA confirmed by a specific inhalation challenge (DA+); 131 symptomatic workers in whom DA was excluded by a negative challenge (DA.); and 147 hexamethylene diisocyanate exposed asymptomatic workers (AWs). As in the Korean study, highly linked CTNNA3 rs7088181 and rs10762058 SNPs (but not rs4378283 and rs1786929) were significantly associated with DA+ when compared with AWs but not in comparison with DA. workers (p . 0.05). After adjusting for potentially confounding variables of age, smoking status, and duration of exposure, minor allele homozygotes of rs7088181 and rs10762058 SNPs were at increased risk for DA compared with AWs (OR = 9.05 [95% CI: 1.69, 48.54] and OR = 6.82 [95% CI: 1.65, 28.24], respectively). In conclusion, we replicated results from the only reported GWAS study of DA demonstrating an association between two closely linked CTNNA3 gene SNPs and DA. These findings lend further support to the clinical relevance of these genotypes in predicting susceptibility to DA and the potential importance of catenins in the disease process. [Description provided by NIOSH]
• Subjects:
  Demography Genetics Lung Lung Diseases Men Occupational Health Race Factors Respiratory System Respiratory Tract Diseases Risk Assessment Risk Factors Safety Women Workplace

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• Keywords:
  Alpha-T Catenin Author Keywords: Diisocyanate Asthma Breathing CTNNA3 Demographic-characteristics Exposure-levels Genes Humans Occupational Asthma Pulmonary-disorders Pulmonary-function Pulmonary-system Pulmonary-system-disorders Racial-factors Respiration Respiratory-system-disorders Risk-factors Sociological-factors Work-environment Workers

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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:
  242-246
• Volume:
  131
• Issue:
  2
• NIOSHTIC Number:
  nn:20042179
• Citation:
  Toxicol Sci 2013 Jan; 131(1):242-246
• Contact Point Address:
  David I. Bernstein, Division of Immunology, Allergy and Rheumatology, University of Cincinnati Department of Internal Medicine, 3255 Eden Avenue, Suite 350, Cincinnati, OH 45267-0563
• Email:
  bernstdd@ucmail.uc.edu
• CAS Registry Number:
  Hexamethylene diisocyanate (CAS RN 822-06-0)
• Federal Fiscal Year:
  2013
• NORA Priority Area:
  Healthcare and Social Assistance
• 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:e6c08996ab1a49fc2bf08575900c04cd33bcfeda925b182dab963be47aa25e751c54782777f0ea6ac3c4d2d6814739e336e60b870a9df7375b950764eb9a5201
• Download URL:
  https://stacks.cdc.gov/view/cdc/194481/cdc_194481_DS1.pdf
• File Type:
  [PDF - 312.40 KB ]