Genetic variants in HLA genes are associated with diisocyanate-induced asthma in exposed workers.
Yucesoy-B; Johnson-VJ; Fluharty-K; Wang-W; Frye-B; Lummus-ZL; Marepalli-R; Bannerman-Thompson-H; Gautrin-D; Malo-J; Cartier-A; Germolec-DR; Luster-MI; Bernstein-DI
Toxicologist 2012 Mar; 126(Suppl 1):348
Diisocyanates, low-molecular weight reactive chemicals extensively used in a variety of industrial processes, are one of the most common causes of occupational asthma. Both immunological and inflammatory mechanisms have been implicated in the development of diisocyanate-induced asthma (DA). A case-control study was conducted to investigate whether genetic variations in genes located within the major histocompatibility complex play a role in susceptibility to DA using a high density SNP map. The study population consisted of 140 workers exposed to diisocyanates (hexamethylene diisocyanate (HDI), methylene diphenyl diisocyanate, and toluene diisocyanate) of which 73 were diagnosed with DA based on a positive specific inhalation challenge and 67 were asymptomatic workers exposed to HDI. Genotype analysis was performed on genomic DNA, using Illumina GoldenGate Genotyping technology. The microarray platform consisted of 2,360 loci with an average spacing of 2 kb. After adjusting for potential confounders, single nucleotide polymorphisms in HLA-E (rs1573294), HLA-B (rs1811157), HLA-DOA (rs3128935), HLA-DQA2 (rs7773955), and HLA-DPB1 (rs928976) showed associations with altered risk of developing DA. Since HLA genes play a key role in the regulation of the immune response, variations in these genes may represent important disease modifiers that contribute to DA susceptibility.
Respiratory-system-disorders; Bronchial-asthma; Cyanates; Pulmonary-function; Lung-irritants; Lung-function; Immune-reaction; Case-studies; Genes; Genetic-factors; Genetics; Employee-exposure; Nucleotides; Nucleic-acids
The Toxicologist. Society of Toxicology 51st Annual Meeting and ToxExpo, March 11-15, 2012, San Francisco, California
University of Cincinnati