Literature DB >> 11258696

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

D L Winterton1, J Kaufman, C V Keener, S Quigley, F M Farin, P V Williams, J Q Koenig.   

Abstract

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 hyperresponsiveness to SO2 observed in some asthmatic patients: the beta2-adrenergic receptor, interleukin-4 (IL-4) receptor alpha subunit, Clara cell secretory protein (CC16), TNF-alpha gene promoter, and first intron of the lymphotoxin alpha (LT-alpha) 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 > or = 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-alpha 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-alpha promoter polymorphism may be associated with mechanisms of asthmatic sensitivity to inhaled SO2.

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Year:  2001        PMID: 11258696     DOI: 10.1016/S1081-1206(10)62697-X

Source DB:  PubMed          Journal:  Ann Allergy Asthma Immunol        ISSN: 1081-1206            Impact factor:   6.347


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