© 2002 American Thoracic Society
DNA Sequence Variants in Epithelium-Specific ETS-2 and ETS-3 Are Not Associated with AsthmaDivision of Pulmonary and Critical Care Medicine; Channing Laboratory, Department of Medicine, Brigham and Women's Hospital; New England Baptist Bone and Joint Institute, Beth Israel Deaconess Medical Center, Harvard Medical School; Department of Environmental Health, Harvard School of Public Health, Boston; Whitehead Genome Center, Massachusetts Institute of Technology, Cambridge; Thermal and Mountain Medicine Division, U.S. Army Research Institute of Environmental Medicine, Natick, Massachusetts; and Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio Correspondence and requests for reprints should be addressed to Eric S. Silverman, M.D., Department of Environmental Health, Harvard School of Public Health, 667 Huntington Avenue, Boston, MA 02115. E-mail: esilverm{at}hsph.harvard.edu Epithelium-specific ETS-2 and ETS-3 are transcription factors that have been proposed as asthma candidate genes. To investigate the association of sequence variants in these genes with asthma, we conducted a case–control association analysis in a sample of 311 white subjects with asthma and 177 white subjects without asthma. Common polymorphisms in these genes were detected by sequencing DNA from 32 cell lines obtained from Coriel (Camden, NJ). Seven noncoding or synonymous single-nucleotide polymorphisms were detected: three in epithelium-specific ETS-2 and four in epithelium-specific ETS-3. Subjects were genotyped at all loci by mass spectroscopy. To ensure the suitability of our control subjects, we also genotyped subjects at 49 unlinked polymorphisms evenly distributed throughout the autosomes and found no evidence of population stratification. Logistic regression adjusted for age and sex suggested a weak association of one epithelium-specific ETS-2 polymorphism with asthma diagnosis (odds ratio = 1.89, 95% confidence interval = 1.13–3.18, p = 0.02). Total serum immunoglobulin E and FEV1 predicted levels were not associated with any of the polymorphisms. Extended haplotyping indicated linkage disequilibrium in these genes; however, no association or epistatic interaction was found. This study suggests that epithelium-specific ETS-2 and ETS-3 genes are unlikely to contain polymorphic loci that have a major impact on asthma susceptibility in our population.
Key Words: genetics • population stratification • polymorphism • Tristan da Cunha • transcription factor This article has been cited by other articles:
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