title: Alpha-tryptase gene variation is associated with levels of circulating IgE and lung function in asthma.
abstract: BACKGROUND
  Tryptase, a major secretory product of human mast cells has been implicated as a key mediator of allergic inflammation. Genetic variation in the tryptases is extensive, and α-tryptase, an allelic variant of the more extensively studied β-tryptase, is absent in substantial numbers of the general population. The degree to which α-tryptase expression may be associated with asthma has not been studied. We have investigated the α-tryptase gene copy number variation and its potential associations with phenotypes of asthma.
  
  
  OBJECTIVE
  Caucasian families (n = 341) with at least two asthmatic siblings (n = 1350) were genotyped for the α-tryptase alleles, using high-resolution melting assays. Standards for the possible α-/β-tryptase ratios were constructed by cloning α-and β-tryptase PCR products to generate artificial templates. Association analysis of asthma affection status and related phenotypes [total and allergen-specific serum IgE, bronchial hyperresponsiveness to methacholine, forced expiratory volume in 1s (FEV1 ) and atopy and asthma severity scores] was undertaken using family-based association tests (FBAT).
  
  
  RESULTS
  Four consistent melting patterns for the α-tryptase genotype were identified with alleles carrying null, one or two copies of the α-tryptase allele. Possessing one copy of α-tryptase was significantly associated with lower serum levels of total and dust mite-specific IgE levels and higher FEV1 measurements, while two copies were related to higher serum concentrations of total and dust mite-specific IgE and greater atopy severity scores.
  
  
  CONCLUSIONS
  Associations of α-tryptase copy number with serum IgE levels, atopy scores and bronchial function may reflect roles for tryptases in regulating IgE production and other processes in asthma.
authors.affiliation: Clinical and Experimental Sciences Unit, Faculty of Medicine, University of Southampton, Southampton, UK; Faculty of Medicine, Tanta University, Tanta, Egypt.
authors.forename: A M
authors.initials: AM
authors.lastname: Abdelmotelb
authors.forename: M J
authors.initials: MJ
authors.lastname: Rose-Zerilli
authors.forename: S J
authors.initials: SJ
authors.lastname: Barton
authors.forename: S T
authors.initials: ST
authors.lastname: Holgate
authors.forename: A F
authors.initials: AF
authors.lastname: Walls
authors.forename: J W
authors.initials: JW
authors.lastname: Holloway
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D000485:Allergens / Q000276:immunology; D000818:Animals; D001249:Asthma / Q000175:diagnosis / Q000209:etiology* / Q000503:physiopathology*; D001483:Base Sequence; D002648:Child; D056915:DNA Copy Number Variations; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology*; D008297:Male; D008969:Molecular Sequence Data; D010641:Phenotype; D039981:Pyroglyphidae / Q000276:immunology; D012129:Respiratory Function Tests; D016415:Sequence Alignment; D053802:Tryptases / Q000737:chemistry / Q000235:genetics*; D055815:Young Adult
chemical_list: D000485:Allergens; D007073:Immunoglobulin E; D053802:Tryptases
keywords: IgE; asthma; gene copy number variation; mast cell; tryptase