DNA Sequence Variants in Epithelium-Specific ETS-2 and ETS-3 Are Not Associated with Asthma

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 whit...

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Bibliographic Details
Published in:American journal of respiratory and critical care medicine 2002-10, Vol.166 (7), p.927-932
Main Authors: Baron, Rebecca M, Palmer, Lyle J, Tantisira, Kelan, Gabriel, Stacey, Sonna, Larry A, Le, Louis, Hallock, Arlene, Libermann, Towia A, Drazen, Jeffrey M, Weiss, Scott T, Silverman, Eric S
Format: Article
Language:English
Subjects:
Adolescent
Adult
Asthma - genetics
Base Sequence - genetics
Biological and medical sciences
Case-Control Studies
Chronic obstructive pulmonary disease, asthma
Female
Forced Expiratory Volume - genetics
Gene Frequency - genetics
Genetic Markers - genetics
Genetic Predisposition to Disease
Genetic Variation - genetics
Genotype
Humans
Immunoglobulin E - blood
Immunoglobulin E - genetics
Linkage Disequilibrium - genetics
Male
Medical sciences
Middle Aged
Multivariate Analysis
Pneumology
Polymorphism, Single Nucleotide - genetics
Predictive Value of Tests
Proto-Oncogene Proteins c-ets
Transcription Factors - genetics
United States
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Summary: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.
ISSN:1073-449X
1535-4970
DOI:10.1164/rccm.200201-048OC