title: Eosinophil cationic protein (ECP) polymorphisms and association with asthma, s-ECP levels and related phenotypes.
abstract: BACKGROUND
  Eosinophil cationic protein (ECP) is a potent cytotoxic secretory protein with bactericidal and antiviral properties. ECP is released by activated eosinophils and regarded as a marker of eosinophilic inflammation. High levels of ECP have been reported in cases of active asthma and other allergic diseases. This study aimed to assess whether three single-nucleotide polymorphisms (SNPs) in the ECP gene (RNASE3) on chromosome 14 q24-q31 or their haplotypes are associated with asthma, allergy, or related phenotypes.
  
  
  METHODS
  The three SNPs -38CA, +371CG and +499CG in RNASE3 and their haplotypes were analyzed for associations with asthma, serum-ECP (s-ECP) levels, allergic sensitization (positive skin-prick test to common allergens), bronchial hyperresponsiveness (BHR) assessed by methacholine inhalation, and serum-IgE (s-IgE) levels in 177 families from Norway and the Netherlands identified through siblings with asthma.
  
  
  RESULTS
  Transmission disequilibrium test (TDT) demonstrated significant associations between the A-G-G haplotype and asthma as well as the specific phenotypes allergic asthma (but not non-allergic asthma), high s-ECP, high s-IgE and BHR, while the C-G-G haplotype was associated with reduced occurrence of these traits. In addition, the -38A allele was associated with high s-ECP levels and allergic asthma.
  
  
  CONCLUSIONS
  The present study suggests that the A-G-G haplotype in the RNASE3 gene influences the development of asthma, in particular, an allergic form of asthma. Furthermore, as the -38CA SNP lies in close vicinity of known intron-regulatory sites, results of SNP analysis suggest that the detected association is possibly linked to a genetic transcriptional control of s-ECP levels.
authors.affiliation: Department of Pediatrics, Ullevål University Hospital, Oslo, Norway.
authors.forename: M C
authors.initials: MC
authors.lastname: Munthe-Kaas
authors.forename: J
authors.initials: J
authors.lastname: Gerritsen
authors.forename: K H
authors.initials: KH
authors.lastname: Carlsen
authors.forename: D
authors.initials: D
authors.lastname: Undlien
authors.forename: T
authors.initials: T
authors.lastname: Egeland
authors.forename: B
authors.initials: B
authors.lastname: Skinningsrud
authors.forename: T
authors.initials: T
authors.lastname: Tørres
authors.forename: K L
authors.initials: KL
authors.lastname: Carlsen
mesh_terms: D000293:Adolescent; D000328:Adult; D001249:Asthma / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology; D016535:Bronchial Hyperreactivity; D001985:Bronchial Provocation Tests; D047150:Eosinophil Cationic Protein / Q000097:blood / Q000235:genetics*; D005260:Female; D005540:Forced Expiratory Flow Rates; D005838:Genotype; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D008297:Male; D016210:Methacholine Chloride / Q000008:administration & dosage; D009426:Netherlands; D009664:Norway; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012882:Skin Tests
chemical_list: D016210:Methacholine Chloride; D007073:Immunoglobulin E; D047150:Eosinophil Cationic Protein; C479220:RNASE3 protein, human