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

https://doi.org/10.1016/S1081-1206(10)62697-XGet rights and content

Background

Individuals with asthma are sensitive to inhaled sulfur dioxide (SO2); 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 SO2.

Objective

It was our objective to determine whether one of the following polymorphism locations linked with asthma is associated with the bronchial hyper-responsiveness to SO2 observed in some asthmatic patients: the β2-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.

Methods

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 SO2. Subjects were classified as SO2 responders if forced expiratory volume in 1 second (FEV1) decreased ≥ 12%. DNA obtained from buccal cell samples was analyzed for genetic polymorphisms.

Results

Of the 62 subjects (21 male and 41 female), 13 had a 12% or greater decrement in FEV1 after SO2 exposure (range +19% to −49%). Response to SO2 was associated with the wild-type allele of the TNF-α promoter polymorphism (12 of 12 SO2 responders versus 28 of 46 nonresponders; P < .05) but with no other polymorphisms. Medication category and atopic status showed no association with SO2 sensitivity.

Conclusions

The wild-type allele of the TNF-α promoter polymorphism may be associated with mechanisms of asthmatic sensitivity to inhaled SO2.

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    This research was supported in part by University of Washington Center Grant P30 ES07033.

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