IL-4 Receptor alpha Polymorphisms May Be a Susceptible Factor for Work-Related Respiratory Symptoms in Bakery Workers

Abstract

Purpose: The IL-4 and IL-4 receptor alpha (IL-4R alpha) genes are the key candidate genes for atopy and asthma susceptibility. Exposure to wheat flour can cause IgE sensitization and respiratory symptoms in bakery workers. Therefore, we hypothesized that IL-4 and IL-4R alpha single nucleotide polymorphisms (SNPs) may be involved in the pathogenic mechanism of baker's asthma. Methods: Clinical and genetic data from 373 bakery workers were analyzed. A survey questionnaire, spirometry, and skin prick tests with wheat flour were performed. Serum-specific IgE, IgG1, and IgG4 to wheat flour were determined using ELISA. Five candidate IL-4 (-729 T>G, 589 T>C, and 33 T>C) and IL-4R alpha (Ile75Val A>G and Gln576Arg A>G) SNPs were genotyped and analyzed. Results: Workers with the G allele of IL-4R alpha Ile75Val A>G had a significantly higher prevalence of work-related lower respiratory symptoms than those with the AA genotype (P=0.004, 16.0% vs. 2.9%). In the skin prick test, workers with the AA genotype of IL-4R alpha Gln576Arg A>G had a significantly higher positive rate to wheat flour (P=0.015, 8.2% vs. 1.1%) than those with AG/GG genotype. No significant associations were found in the three genetic polymorphisms of IL-4. For the predicted probabilities, workers with the AA genotype of Gln576Arg A>G had a higher prevalence of IgG1 and IgG4 in response to wheat flour, according to increased exposure intensity (P=0.001 for IgG1 and P=0.003 for IgG4). Conclusions: These findings suggest that the IL-4R alpha Ile75Val and Gln576Arg polymorphisms may be associated with work-related respiratory symptom development.