Association of Tumor Necrosis Factor-Alpha and Interleukin-1 Gene Polymorphisms with Silicosis

Details

• Personal Author:
  Burleson GR ; Landsittel DP ; Luster MI ; McKinstry M ; Sharp DS ; Simeonova P ; Vallyathan V ; Weston A ; Yucesoy, Berran
• Description:
  Silicosis, an interstitial lung disease prevalent among miners, sand blasters, and quarry workers, is manifested as a chronic inflammatory response leading to severe pulmonary fibrotic changes. Proinflammatory cytokines, such as TNFalpha and IL-1, produced in the lung by type II epithelial cells and alveolar macrophages, have been strongly implicated in the formation of these lesions. Recently, a number of single nucleotide polymorphisms (SNPs), which quantitatively affect mRNA synthesis, have been identified in the TNFalpha promoter and IL-1 gene cluster and their frequency is associated with certain chronic inflammatory diseases. To assess the role of these SNPs in silicosis, we examined their frequency in 325 ex-miners with moderate and severe silicosis and 164 miners with no lung disease. The odds ratio of disease for carriers of the minor variant, TNFalpha (-238), was markedly higher for severe silicosis (4.0) and significantly lower for moderate silicosis (0.52). Regardless of disease severity, the odds ratios of disease for carriers of the IL-1RA (+2018) or TNFalpha (-308) variants were elevated. There were no significant consistent differences in the distribution of the IL-1alpha (+4845) or IL-1beta (+3953) variants with respect to disease status. In addition, several significant gene-gene and gene-gene-environment interactions were observed. Different associations between moderate cases and controls versus severe cases and controls were also observed in a number of these multigene comparisons. These studies suggest that gene-environment interactions involving cytokine polymorphisms play a significant role in silicosis by modifying the extent of and susceptibility to disease. [Description provided by NIOSH]
• Subjects:
  Demography Epidemiology Genetics Lung Diseases Occupational Health Respiratory Tract Diseases Safety Silicosis
• Keywords:
  Author Keywords: Silicosis Demographic-characteristics Genes Genetic-factors Interleukin-1 Lung-disease Polymorphism Pulmonary-system-disorders Respiratory-system-disorders Tumor Necrosis Factor-a
• ISSN:
  0041-008X
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  North Carolina ; OSHA Region 3 ; OSHA Region 4 ; 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:
  75-82
• Volume:
  172
• Issue:
  1
• NIOSHTIC Number:
  nn:20021939
• Citation:
  Toxicol Appl Pharmacol 2001 Apr; 172(1):75-82
• Contact Point Address:
  Toxicology and Molecular Biology Branch, National Institute for Occupational Safety and Health, 1095 Willowdale Road, Morgantown, West Virginia 26505, USA
• CAS Registry Number:
  Quartz (SiO2) (CAS RN 14808-60-7)
• Federal Fiscal Year:
  2001
• Peer Reviewed:
  True
• Source Full Name:
  Toxicology and Applied Pharmacology
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:1f101a9352f405ce3fc4ccff9c2c0db651980efa09d257421e82ebfd6f90929cf8928f0d484ab0b52786c8e1762342d4210e5f001aee79da3b39c5f0428ca18c
• Download URL:
  https://stacks.cdc.gov/view/cdc/199013/cdc_199013_DS1.pdf
• File Type:
  [PDF - 78.08 KB ]