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

Details

• Alternative Title:
  J Immunotoxicol
• Personal Author:
  Yucesoy, Berran ; Kashon, Michael L. ; Johnson, Victor J. ; Lummus, Zana L. ; Fluharty, Kara ; Gautrin, Denyse ; Cartier, André ; Boulet, Louis-Philippe ; Sastre, Joaquin ; Quirce, Santiago ; Tarlo, Susan M. ; Cruz, Maria-Jesus ; Munoz, Xavier ; Luster, Michael I. ; Bernstein, David I.
• 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 (TNFα, IL1α, IL1β, 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 5' 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 TNFα 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 TNFα, TGFB1, PTGS1 and PTGS2 genes contribute to DA susceptibility.
• Subjects:
  Adult Asthma, Occupational Case-Control Studies Cyclooxygenase 1 Cyclooxygenase 2 DNA Mutational Analysis Environmental Exposure Female Genetic Association Studies Genetic Predisposition To Disease Genotype Humans Inflammation Male Polymorphism, Single Nucleotide Toluene 2,4-Diisocyanate Transforming Growth Factor Beta1 Tumor Necrosis Factor-alpha

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• Keywords:
  Cytokine Diisocyanates Inflammation Occupational Asthma Single Nucleotide Polymorphism (SNP)
• Source:
  J Immunotoxicol. 13(1):119-126
• Pubmed ID:
  25721048
• Pubmed Central ID:
  PMC4814713
• Document Type:
  Journal Article
• Funding:
  R01 OH008795/OH/NIOSH CDC HHSUnited States/ ; AES12007001-1-0-6/PHS HHSUnited States/ ; R01 OH 008795/OH/NIOSH CDC HHSUnited States/
• Volume:
  13
• Issue:
  1
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha-512:cdebecc9ee8f8e183bbc5e2fd6139c72486782583929cb1e41659883bf1377041b519830213cfd65b1458f655666fa6f15ddae6997d53200a0e84b64e5d099bc
• Download URL:
  https://stacks.cdc.gov/view/cdc/38758/cdc_38758_DS1.pdf
• File Type:
  [PDF - 393.37 KB ]