Diisocyanate asthma and gene-environment interactions with IL4RA, CD-14 and IL-13 genes

David I. Bernstein, Ning Wang, Paloma Campo, Ranajit Chakraborty, Andrew Smith, André Cartier, Louis Philippe Boulet, Jean Luc Malo, Berran Yucesoy, Michael Luster, Susan M. Tarlo, Gurjit K.Khurana Hershey

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Abstract

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.

Original languageEnglish
Pages (from-to)800-806
Number of pages7
JournalAnnals of Allergy, Asthma and Immunology
Volume97
Issue number6
DOIs
StatePublished - Dec 2006

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    Bernstein, D. I., Wang, N., Campo, P., Chakraborty, R., Smith, A., Cartier, A., Boulet, L. P., Malo, J. L., Yucesoy, B., Luster, M., Tarlo, S. M., & Hershey, G. K. K. (2006). Diisocyanate asthma and gene-environment interactions with IL4RA, CD-14 and IL-13 genes. Annals of Allergy, Asthma and Immunology, 97(6), 800-806. https://doi.org/10.1016/S1081-1206(10)60972-6