title: 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.
  
  
  CONCLUSIONS
  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.affiliation: Hôpital Laval, Université Laval, Quebec, Canada.
authors.forename: Karine
authors.initials: K
authors.lastname: Tremblay
authors.forename: Denise
authors.initials: D
authors.lastname: Daley
authors.forename: Annie
authors.initials: A
authors.lastname: Chamberland
authors.forename: Mathieu
authors.initials: M
authors.lastname: Lemire
authors.forename: Alexandre
authors.initials: A
authors.lastname: Montpetit
authors.forename: Michel
authors.initials: M
authors.lastname: Laviolette
authors.forename: Arthur W
authors.initials: AW
authors.lastname: Musk
authors.forename: Alan L
authors.initials: AL
authors.lastname: James
authors.forename: Moira
authors.initials: M
authors.lastname: Chan-Yeung
authors.forename: Allan
authors.initials: A
authors.lastname: Becker
authors.forename: Anita L
authors.initials: AL
authors.lastname: Kozyrskyj
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Sandford
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Hudson
authors.forename: Peter D
authors.initials: PD
authors.lastname: Paré
authors.forename: Catherine
authors.initials: C
authors.lastname: Laprise
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001093:Arachidonate 15-Lipoxygenase / Q000235:genetics* / Q000378:metabolism; D001249:Asthma / Q000235:genetics* / Q000276:immunology; D016535:Bronchial Hyperreactivity / Q000235:genetics*; D002648:Child; D005260:Female; D015870:Gene Expression; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000235:genetics* / Q000276:immunology; D008168:Lung / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
chemical_list: D018950:Lipopolysaccharide Receptors; D001093:Arachidonate 15-Lipoxygenase