TY - JOUR
T1 - Diisocyanate asthma and gene-environment interactions with IL4RA, CD-14 and IL-13 genes
AU - Bernstein, David I.
AU - Wang, Ning
AU - Campo, Paloma
AU - Chakraborty, Ranajit
AU - Smith, Andrew
AU - Cartier, André
AU - Boulet, Louis Philippe
AU - Malo, Jean Luc
AU - Yucesoy, Berran
AU - Luster, Michael
AU - Tarlo, Susan M.
AU - Hershey, Gurjit K.Khurana
N1 - Funding Information:
* Department of Internal Medicine, Division of Immunology, University of Cincinnati Medical Center, Cincinnati, Ohio. † Department of Pediatrics, Division of Allergy and Immunology, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio. ‡ Department of Pediatrics, Division of Human Genetics, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio. § Department of Environmental Health, Center for Genome Information, University of Cincinnati Medical Center, Cincinnati, Ohio. ‖ Hôpital du Sacré Coeur de Montréal, Montréal, Quebec, Canada. ¶ Institut de Cardiologie et de Pneumologie de L’Université Laval, Hôpital Laval, Sainte-Foy, Québec, Canada. # Toxicology and Molecular Biology Branch, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Morgantown, West Virginia. ** Gage Occupational and Environmental Health Unit, University of Toronto, Toronto, Ontario. This study was supported by National Institute of Health grant R01AI46652-01A1 (Dr Hershey); National Institute for Occupational Safety and Health grant R01 OH03519-01 (Dr Bernstein); IAG from the National Institute of Environmental Health Sciences to the National Institute for Occupational Safety and Health (Y-ES-0001 Clinical Immunotoxicity of Workplace Xenobiotics); FIS/Fulbright Scholarship (Dr Campo); and National Institute of Allergy and Infectious Disease grant T32 AI 060515-01 (Dr Smith). Received for publication June 7, 2006. Accepted for publication in revised form August 23, 2006.
PY - 2006/12
Y1 - 2006/12
N2 - Background: Diisocyanate asthma (DA) affects 2% to 10% of exposed workers, yet the pathogenetic mechanisms underlying this disorder remain ill defined. Objective: To determine if specific single nucleotide polymorphisms (SNPs) of interleukin 4 receptor α (ILARA), IL-13, and CD14 promoter genes are associated with DA. Methods: Sixty-two workers with DA confirmed by specific inhalation challenge (SIC) and 75 diisocyanate-exposed, SIC-negative workers were analyzed for SNPs associated with IL4RA, IL-13, and CD14 promoter genes. Results: No associations were found with individual SNPs and DA. When stratified according to specific diisocyanate exposure, a significant association was found between IL4RA (I50V) II and DA among individuals exposed to hexamethylene diisocyanate (HDI) (odds ratio [OR], 3.29; 95% confidence interval [CI], 1.33-8.14; P = .01) only. Similarly, the ILARA (I50V) II and IL-13 (R110Q) RR combination was significantly associated with DA in HDI-exposed workers (OR, 4.13; 95% CI, 1.35-12.68; P = .01), as was the IL4RA (I50V) II and CD14 (C159T) CT genotype combination (OR, 5.2; 95% CI, 1.82-14.88; P = .002) and the triple genotype combination ILARA (I50V) II, IL-13 (R110Q) RR, and CD14 (C159T) CT (OR, 6.4; 95% CI, 1.57-26.12; P = .01). Conclusions: Gene-environmental interactions may contribute to the pathogenesis of DA, and gene-gene interactions may modulate this relationship.
AB - Background: Diisocyanate asthma (DA) affects 2% to 10% of exposed workers, yet the pathogenetic mechanisms underlying this disorder remain ill defined. Objective: To determine if specific single nucleotide polymorphisms (SNPs) of interleukin 4 receptor α (ILARA), IL-13, and CD14 promoter genes are associated with DA. Methods: Sixty-two workers with DA confirmed by specific inhalation challenge (SIC) and 75 diisocyanate-exposed, SIC-negative workers were analyzed for SNPs associated with IL4RA, IL-13, and CD14 promoter genes. Results: No associations were found with individual SNPs and DA. When stratified according to specific diisocyanate exposure, a significant association was found between IL4RA (I50V) II and DA among individuals exposed to hexamethylene diisocyanate (HDI) (odds ratio [OR], 3.29; 95% confidence interval [CI], 1.33-8.14; P = .01) only. Similarly, the ILARA (I50V) II and IL-13 (R110Q) RR combination was significantly associated with DA in HDI-exposed workers (OR, 4.13; 95% CI, 1.35-12.68; P = .01), as was the IL4RA (I50V) II and CD14 (C159T) CT genotype combination (OR, 5.2; 95% CI, 1.82-14.88; P = .002) and the triple genotype combination ILARA (I50V) II, IL-13 (R110Q) RR, and CD14 (C159T) CT (OR, 6.4; 95% CI, 1.57-26.12; P = .01). Conclusions: Gene-environmental interactions may contribute to the pathogenesis of DA, and gene-gene interactions may modulate this relationship.
UR - http://www.scopus.com/inward/record.url?scp=33845952668&partnerID=8YFLogxK
U2 - 10.1016/S1081-1206(10)60972-6
DO - 10.1016/S1081-1206(10)60972-6
M3 - Article
C2 - 17201240
AN - SCOPUS:33845952668
SN - 1081-1206
VL - 97
SP - 800
EP - 806
JO - Annals of Allergy, Asthma and Immunology
JF - Annals of Allergy, Asthma and Immunology
IS - 6
ER -