A polymorphism of MS4A2 (-109T> C) encoding the ?-chain of the high-affinity immunoglobulin E receptor (Fc?R1?) is associated with a susceptibility to aspirin-intolerant asthma

BACKGROUND AND OBJECTIVE: The MS4A2 gene, the ? chain of the high-affinity receptor for immunoglobulin (Ig)E, has previously been linked to atopy and asthma. The beta-chain of FcepsilonR1 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 Fc?R1? gene (Fc?R1?-109T> C and FcepsilonR1? E237G) are associated with aspirin-intolerant asthma (AIA). The MS4A2 gene polymorphisms (Fc?R1?-109T> C and Fc?R1? 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 Fc?R1?-109T> C and E237G polymorphisms were not significantly associated with the pathogenesis of AIA. However, Fc?R1?-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 Fc?R1?-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 approximately 35.229 for AIA vs. NC). In addition, luciferase reporter assays also showed that the Fc?R1?-109T allele was associated with higher promoter activity of MS4A2 in both RBL-2H3 and A549 cell lines. CONCLUSION: Fc?R1?-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