title: Genetic variants in TNFα, TGFB1, PTGS1 and PTGS2 genes are associated with diisocyanate-induced asthma.
abstract: 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.
authors.affiliation: a Division of Immunology , Allergy and Rheumatology, University of Cincinnati College of Medicine , Cincinnati , OH , USA .|b CDC/National Institute for Occupational Safety and Health, Health Effects Laboratory Division , Morgantown , WV , USA .
authors.forename: Berran
authors.initials: B
authors.lastname: Yucesoy
authors.affiliation: b CDC/National Institute for Occupational Safety and Health, Health Effects Laboratory Division , Morgantown , WV , USA .
authors.forename: Michael L
authors.initials: ML
authors.lastname: Kashon
authors.affiliation: c BRT-Burleson Research Technologies , Morrisville , NC , USA .
authors.forename: Victor J
authors.initials: VJ
authors.lastname: Johnson
authors.affiliation: a Division of Immunology , Allergy and Rheumatology, University of Cincinnati College of Medicine , Cincinnati , OH , USA .
authors.forename: Zana L
authors.initials: ZL
authors.lastname: Lummus
authors.affiliation: b CDC/National Institute for Occupational Safety and Health, Health Effects Laboratory Division , Morgantown , WV , USA .
authors.forename: Kara
authors.initials: K
authors.lastname: Fluharty
authors.affiliation: d Université de Montréal, Hôpital du Sacré-Coeur de Montréal , Montreal , Quebec , Canada .
authors.forename: Denyse
authors.initials: D
authors.lastname: Gautrin
authors.affiliation: d Université de Montréal, Hôpital du Sacré-Coeur de Montréal , Montreal , Quebec , Canada .
authors.forename: André
authors.initials: A
authors.lastname: Cartier
authors.affiliation: e Université Laval, Hôpital Laval , Sainte-Foy , Québec , Canada .
authors.forename: Louis-Philippe
authors.initials: LP
authors.lastname: Boulet
authors.affiliation: f Department of Allergy , Fundación Jiménez Díaz and CIBER de Enfermedades Respiratorias CIBERES , Madrid , Spain .
authors.forename: Joaquin
authors.initials: J
authors.lastname: Sastre
authors.affiliation: g Department of Allergy , Hospital La Paz-IdiPAZ and CIBER de Enfermedades Respiratorias CIBERES , Madrid , Spain .
authors.forename: Santiago
authors.initials: S
authors.lastname: Quirce
authors.affiliation: h Department of Medicine , and.|i Dalla Lana School of Public Health, University of Toronto , Toronto , Ontario , Canada .
authors.forename: Susan M
authors.initials: SM
authors.lastname: Tarlo
authors.affiliation: j Hospitals Vall D'Hebron, Barcelona and CIBER de Enfermedades Respiratorias CIBERES , Madrid , Spain , and.
authors.forename: Maria-Jesus
authors.initials: MJ
authors.lastname: Cruz
authors.affiliation: j Hospitals Vall D'Hebron, Barcelona and CIBER de Enfermedades Respiratorias CIBERES , Madrid , Spain , and.
authors.forename: Xavier
authors.initials: X
authors.lastname: Munoz
authors.affiliation: k West Virginia University, School of Public Health , Morgantown , WV , USA.
authors.forename: Michael I
authors.initials: MI
authors.lastname: Luster
authors.affiliation: a Division of Immunology , Allergy and Rheumatology, University of Cincinnati College of Medicine , Cincinnati , OH , USA .
authors.forename: David I
authors.initials: DI
authors.lastname: Bernstein
mesh_terms: D000328:Adult; D059366:Asthma, Occupational / Q000139:chemically induced / Q000276:immunology* / Q000378:metabolism*; D016022:Case-Control Studies; D051545:Cyclooxygenase 1 / Q000235:genetics; D051546:Cyclooxygenase 2 / Q000235:genetics; D004252:DNA Mutational Analysis; D004781:Environmental Exposure / Q000009:adverse effects; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007249:Inflammation / Q000235:genetics; D008297:Male; D020641:Polymorphism, Single Nucleotide; D014051:Toluene 2,4-Diisocyanate / Q000276:immunology*; D053773:Transforming Growth Factor beta1 / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D014051:Toluene 2,4-Diisocyanate; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human
keywords: Cytokine; diisocyanates; inflammation; occupational asthma; single nucleotide polymorphism (SNP)