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

Authors: Bernstein, David I.; Wang, Ning; Campo, Paloma; Chakraborty, Ranajit; Smith, Andrew; Cartier, André; Boulet, Louis-Philippe; Malo, Jean-Luc; Yucesoy, Berran; Luster, Michael; Tarlo, Susan M.; Hershey, Gurjit K.K.h.u.r.a.n.a.

Source: Annals of Allergy, Asthma and Immunology, Volume 97, Number 6, December 2006 , pp. 800-806(7)

Publisher: American College of Allergy, Asthma, & Immunology

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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 (IL4RA), 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 IL4RA (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 IL4RA (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.

Document Type: Original article

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