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

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.

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.

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.

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.