A polymorphism of MS4A2 (−109T>C) encoding the β-chain of the high-affinity immunoglobulin E receptor (FcɛR1β) is associated with a susceptibility to aspirin-intolerant asthma


Hae-Sim Park, Department of Allergy and Rheumatology,
Ajou University School of Medicine,
Paldalgu Wonchondong San-5,
Suwon 442-721, Korea.
E-mail: hspark@ajou.ac.kr


Background and objective The MS4A2 gene, the β chain of the high-affinity receptor for immunoglobulin (Ig)E, has previously been linked to atopy and asthma. The β-chain of FcɛR1 enhances receptor maturation and signal transduction capacity, leading to the release of proinflammatory mediators and cytokines that can exacerbate the symptom of asthma. This study was performed to evaluate whether two genetic polymorphisms of the FcɛR1β gene (FcɛR1β−109T>C and FcɛR1β E237G) are associated with aspirin-intolerant asthma (AIA).

Methods The MS4A2 gene polymorphisms (FcɛR1β−109T>C and FcɛR1β E237G) were determined by SNP-IT™ assays in patients with AIA (N=164), aspirin-tolerant asthma (ATA, N=144) and normal controls (NC, N=264) recruited from a Korean population.

Results The genotype frequencies of FcɛR1β−109T>C and E237G polymorphisms were not significantly associated with the pathogenesis of AIA. However, FcɛR1β−109T>C polymorphism was significantly associated with the presence of specific IgE to Staphylococcal enterotoxin B (SEB); the number of subjects carrying both homozygous TT genotype of FcɛR1β−109T>C and specific IgE to SEB was significantly higher in the AIA group when compared with the other control groups (P=0.01, odds ratio (OR)=7.723, 95% confidence interval (CI)=1.327–39.860 for AIA vs. ATA; P=0.02, OR=6.364, 95% CI=1.149∼35.229 for AIA vs. NC). In addition, luciferase reporter assays also showed that the FcɛR1β−109T allele was associated with higher promoter activity of MS4A2 in both RBL-2H3 and A549 cell lines.

Conclusion FcɛR1β−109T>C polymorphism may increase expression of MS4A2 by mast cells, leading to enhanced release of proinflammatory mediators in the asthmatic airway, contributing to increased susceptibility to AIA.