Genetic polymorphisms as biomarkers of sensitivity to inhaled sulfur dioxide in subjects with asthma.
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.
Department of Environmental Health, University of Washington, Seattle 98195, USA.
D L
DL
Winterton
J
J
Kaufman
C V
CV
Keener
S
S
Quigley
F M
FM
Farin
P V
PV
Williams
J Q
JQ
Koenig
D000280:Administration, Inhalation; D000328:Adult; D000483:Alleles; D001249:Asthma / Q000235:genetics* / Q000276:immunology*; D015415:Biomarkers / Q000032:analysis*; D005260:Female; D005838:Genotype; D006801:Humans; D007114:Immunization; D008297:Male; D008875:Middle Aged; D009061:Mouth Mucosa / Q000737:chemistry; D011110:Polymorphism, Genetic / Q000235:genetics; D013458:Sulfur Dioxide / Q000008:administration & dosage*
D015415:Biomarkers; D013458:Sulfur Dioxide