Student Research: Debra Winterton

Polymorphisms as Biomarkers for Sensitivity to Inhaled Sulfur Dioxide in Subjects with Asthma
1999
Faculty Advisor: 

Abstract

It has been shown that people with asthma are a sensitive subpopulation to inhaled sulfur dioxide (SO2); decrements in pulmonary function occur in subjects after exposure to low concentrations even for a short duration of time. There is a great amount of inter-individual variation in response to SO2. Genetics is one factor in the pathophysiology of asthma and may be a factor in bronchial hyperresponsiveness (BHR) to SO2. Variant alleles may serve as biomarkers for this BHR. Those of interest in this study are located in he coding regions for the B2-adrenergic receptor, the interluekin-4 (IL-4) receptor subunit, the Clara cell secretory protein (CC16), the tumor necrosis factor alpha (TNFa) gene promoter, adn the first intron of the lymphotoxin alpha (LT-a) gene. Polymorphisms of all of the above have been the focus of other asthma studies. In an attempt to identify risk factorsfor variation in response, an SO2 screening study was conducted. DNA for he polymorphism assays was obtained from buccal cells. The subjects were volunteers, all of whom have physician-diagnosed asthma. Spirometry, a technique to measure pulmonary function, was performed both before and after a ten-minute exposure to 0.5-ppm concentration of SO2. In the 63 subjects, differences in forced expiratory volume in 1 second (FEV1) before and after SO2 exposure range from +19% to -49%. The Molecular Biomarker Lab in the Center for Ecogenetics and Environmental Health at the University of Washington analyzed the DNA for the various polymorphisms. Chi Square tests evaluated significant differences in the odds ratios of the various alleles between the responders and non-responders to SO2. Response to SO2 was associated with the wild type allele of the TNFa promoter polymorphism but no other polymorphisms. Medication category and atopic status showed no assocation with SO2 sensitivity; however, 92% of the responders were atopic.