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.
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: Bohao Chen; Tamson V Moore; Zhenping Li; Anne I Sperling; Chunling Zhang; Jorge Andrade; Alex Rodriguez; Neil Bahroos; Yong Huang; Edward E Morrisey; Peter J Gruber; Julian Solway Journal: Am J Respir Cell Mol Biol Date: 2014-04 Impact factor: 6.914
Authors: Kate V Everett; Barry A Chioza; Christina Georgoula; Ashley Reece; R Mark Gardiner; Eddie M K Chung Journal: Hum Genet Date: 2009-12 Impact factor: 4.132
Authors: Jinming Zhao; Ben Maskrey; Silvana Balzar; Kazuyuki Chibana; Anthony Mustovich; Haizhen Hu; John B Trudeau; Valerie O'Donnell; Sally E Wenzel Journal: Am J Respir Crit Care Med Date: 2009-02-12 Impact factor: 21.405
Authors: Anja Rogler; Sabine Hoja; Eileen Socher; Elke Nolte; Sven Wach; Wolf Wieland; Ferdinand Hofstädter; Peter J Goebell; Bernd Wullich; Arndt Hartmann; Robert Stoehr Journal: Int J Clin Exp Pathol Date: 2013-09-15