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.
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