Genetic polymorphisms as biomarkers of sensitivity to inhaled sulfur dioxide in subjects with asthma

Individuals with asthma are sensitive to inhaled sulfur dioxide (SO 2); decrements in pulmonary function occur after exposure to low concentrations even for a short duration of time. There is a great amount of interindividual variation in response to SO 2. It was our objective to determine whether one of the following polymorphism locations linked with asthma is associated with the bronchial hyper-responsiveness to SO 2 observed in some asthmatic patients: the β 2-adrenergic receptor, interleukin-4 (IL-4) receptor α subunit, Clara cell secretory protein (CC16), TNF-α gene promoter, and first intron of the lymphotoxin α (LT-α) gene. Subjects were volunteers with physician-diagnosed asthma requiring regular asthma medication. Spirometry was performed before and after a 10-minute exposure to 0.5 ppm SO 2. Subjects were classified as SO 2 responders if forced expiratory volume in 1 second (FEV 1) decreased ≥ 12%. DNA obtained from buccal cell samples was analyzed for genetic polymorphisms. Of the 62 subjects (21 male and 41 female), 13 had a 12% or greater decrement in FEV 1 after SO 2 exposure (range +19% to −49%). Response to SO 2 was associated with the wild-type allele of the TNF-α promoter polymorphism (12 of 12 SO 2 responders versus 28 of 46 nonresponders; P < .05) but with no other polymorphisms. Medication category and atopic status showed no association with SO 2 sensitivity. The wild-type allele of the TNF-α promoter polymorphism may be associated with mechanisms of asthmatic sensitivity to inhaled SO 2.