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

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• 作者：Karine Tremblay ; Denise Daley ; Annie Chamberl ; Mathieu Lemire ; Alex ; re Montpetit ; Michel Laviolette ; Arthur W. Musk ; Alan L. James ; Moira Chan-Yeung ; Allan Becker ; Anita L. Kozyrskyj ; Andrew J. S ; ford ; Thomas J. Hudson ; Peter D. Paré ; Catherine Laprise
• 关键词：Asthma ; microarrays expression profiling ; candidate genes ; genetic association study ; tagging single nucleotide polymorphism ; 15-lipoxygenase
• 刊名：Journal of Allergy and Clinical Immunology
• 出版年：2008
• 出版时间：September 2008
• 年：2008
• 卷：122
• 期：3
• 页码：529-536.e17
• 全文大小：3358 K

文摘

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 (r² > 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.