IngentaConnect Eosinophil cationic protein (ECP) polymorphisms and association w...

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. Conclusion:

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.

Keywords: allergy; asthma; ECP polymorphisms; eosinophilic cationic protein; genetic analysis

Document Type: Research article

DOI: 10.1111/j.1398-9995.2007.01327.x

Affiliations: 1: University Medical Centre Groningen, Department of Pediatrics, University of Groningen, Groningen, The Netherlands 2: Department of Medical Genetics, Ullevål University Hospital, Oslo, Norway 3: Institute of Medical Genetics, Ullevål University Hospital, University of Oslo, Oslo, Norway 4: Voksentoppen, Department of Pediatrics, Rikshospitalet-Radiumhospitalet Medical Center, Oslo, Norway

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Eosinophil cationic protein (ECP) polymorphisms and association with asthma, s-ECP levels and related phenotypes