Diisocyanate asthma and gene-environment interactions with IL4RA, CD-14, and IL-13 genes.
Bernstein-DI; Wang-N; Campo-P; Chakraborty-R; Smith-A; Cartier-A; Boulet-LP; Malo-JL; Yucesoy-B; Luster-M; Tarlo-SM; Hershey-GKK
Ann Allergy, Asthma, & Immun 2006 Dec; 97(6):800-806
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 alpha (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 (150V) 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 (150V) 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 (150V) II and CD14 (C159T) CT genotype combination (OR, 5.2; 95% CI, 1.82-14.88; P = .002) and the triple genotype combination IL4RA (150V) 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.
Pathogenesis; Pathogenicity; Pathogens; Pathomorphology; Gerontology; Chemical-hypersensitivity; Chemical-indicators; Chemical-properties; Chemical-reactions; Chemoreceptors
GKK Hershey, Childrens Hosp, Med Ctr, Dept Pediat, Div Allergy & Immunol, 3333 Burnet Ave, Cincinnati, OH 45229
Disease and Injury: Asthma and Chronic Obstructive Pulmonary Disease
Annals of Allergy, Asthma, and Immunology