Genetic variation in immune signaling genes differentially expressed in asthmatic lung tissues.

Abstract

BACKGROUND:

Eight genes in the immune signaling pathway shown to be differentially expressed in asthmatic lung biopsy specimens in a previous microarray experiment were selected as candidate genes for asthma susceptibility.

OBJECTIVE:

We sought to perform an association study with these genes and asthma-related phenotypes in 3 independent Canadian familial asthma collections and 1 Australian asthma case-control study.

METHODS:

Tagging single nucleotide polymorphisms were selected by using the HapMap public database (r(2) > 0.8; minor allele frequency >0.10) and genotyped with the Illumina platform. Family-based association and trend tests for asthma, atopy, airway hyperresponsiveness, and allergic asthma phenotypes were done in each sample, correcting for multiple testing.

RESULTS:

Uncorrected associations with polymorphisms within 7 genes were detected with 1 or more of the phenotypes in 1 or more of the 4 populations (.001 <P < .05). After correction, the 15-lipoxygenase (15-LO) associations with airway hyperresponsiveness and allergic asthma remained significant in 2 Canadian samples (corrected P = .022 and .049, respectively), and the association of the CD14 antigen with asthma remained significant in 1 Canadian sample (corrected P = .042). In both cases a protective effect of the minor alleles was observed.

CONCLUSION:

Expression profiling studies are a useful way to identify candidate genes for asthma because this approach has led to the first report of an association with 15-LO in 2 independent populations. Because 15-LO is involved in anti-inflammatory processes, further functional and clinical investigation of the role of this biologic pathway in asthma is warranted.

• Authors: Karine Tremblay, Denise Daley, Annie Chamberland, Mathieu Lemire, Alexandre Montpetit, Michel Laviolette, Arthur W Musk, Alan L James, Moira Chan-Yeung, Allan Becker, Anita L Kozyrskyj, Andrew J Sandford, Thomas J Hudson, Peter D Paré, Catherine Laprise
• Journal: The Journal of allergy and clinical immunology (J Allergy Clin Immunol) Vol. 122 Issue 3 Pg. 529-36.e17 (Sep 2008) ISSN: 1097-6825 [Electronic] United States
• PMID: 18774388 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Lipopolysaccharide Receptors
• Arachidonate 15-Lipoxygenase

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Arachidonate 15-Lipoxygenase (genetics, metabolism)
• Asthma (genetics, immunology)
• Bronchial Hyperreactivity (genetics)
• Child
• Female
• Gene Expression
• Genetic Variation
• Genotype
• Humans
• Lipopolysaccharide Receptors (genetics, immunology)
• Lung (immunology, metabolism)
• Male
• Middle Aged
• Polymorphism, Single Nucleotide