A genetic effect of IL-5 receptor alpha polymorphism in patients with aspirin-exacerbated respiratory disease.
- Author:
Purevsuren LOSOL
1
;
Seung Hyun KIM
;
Yoo Seob SHIN
;
Young Min YE
;
Hae Sim PARK
Author Information
1. Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, South Korea. hspark@ajou.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
aspirin-exacerbated respiratory disease;
eosinophilic inflammation;
IL5RA;
polymorphism;
staphylococcal superantigen
- MeSH:
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
- From:Experimental & Molecular Medicine
2013;45(3):e14-
- CountryRepublic of Korea
- Language:English
-
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.
