Exp Mol Med.  2013 Mar;45(3):e14.

A genetic effect of IL-5 receptor alpha polymorphism in patients with aspirin-exacerbated respiratory disease

• Losol P
• Kim SH
• Shin YS
• Ye YM
• Park HS

Abstract

Persistent eosinophil activation in both the upper and lower airway mucosa is a central feature of aspirin-exacerbated respiratory disease (AERD). Eosinophil activation and survival are profoundly influenced by interleukin 5 (IL-5) and its receptor, IL-5R. In patients susceptible to allergic disorders, IL-5 receptor alpha (IL5RA) polymorphisms have been reported; however, an association with AERD remains unclear. We hypothesize that IL5RA polymorphisms may contribute to eosinophil activation in AERD patients. We recruited 139 AERD patients, 171 aspirin-tolerant asthma patients and 160 normal controls. IL5RA polymorphisms (-5993G>A, -5567C>G and -5091G>A) were genotyped and functional activity of polymorphism was assessed by luciferase reporter assay and electrophoretic mobility shift assay (EMSA). There was no significant difference in the genotype frequency of the three polymorphisms among the three groups. AERD patients carrying the AA genotype at -5993G>A had a significantly higher presence of serum-specific immunoglobulin E (IgE) to staphylococcal enterotoxin A (P=0.008) than those with the GG/GA genotype. In vitro, the -5993A allele had a higher promoter activity compared with the -5993G allele in human mast cell (HMC-1; P=0.030) and human promyelocytic leukemia (HL-60; P=0.013) cells. In EMSA, a -5993A probe produced a specific shifted band than the -5993G had. These findings suggest that a functional polymorphism in IL5RA may contribute to eosinophil and mast cell activation along with specific IgE responses to staphylococcal enterotoxin A in AERD patients.

Keyword

aspirin-exacerbated respiratory disease; eosinophilic inflammation; IL5RA; polymorphism; staphylococcal superantigen

MeSH Terms

Adult
Aspirin/*adverse effects
Electrophoretic Mobility Shift Assay
Female
Gene Frequency/genetics
Humans
Interleukin-5 Receptor alpha Subunit/*genetics
Male
Middle Aged
Phenotype
Polymorphism, Single Nucleotide/*genetics
Respiration Disorders/*chemically induced/*genetics
Transcription, Genetic
Interleukin-5 Receptor alpha Subunit
Aspirin