Analysis of high-affinity IgE receptor (FcεR1) polymorphisms in patients with aspirin-intolerant chronic urticaria

Chronic urticaria (CU) associated with aspirin sensitivity, termed aspirin-intolerant CU (AICU), is a common condition in the general population. The genetic mechanism of AICU still is not fully understood. We investigated genetic polymorphisms of FcεR1β and FcεR1γ in patients with CU including AICU and aspirin-tolerant CU (ATCU) by analyzing the genotypes and haplotypes of four subsets of FcεR1 genes in association with various clinical parameters. Four polymorphisms of FcεR1 (FceR1β -109T>C, FcεR1β E237G, FcεR1γ -237A>G, and FcεR1γ -54G>T) were genotyped in 119 AICU patients and compared with 154 patients with ATCU and 224 normal healthy controls (NCs). No significant differences were observed with respect to the allele and genotype frequencies of all four FcεR1 single-nucleotide polymorphisms (SNPs; p > 0.05) in CU including AICU and ATCU patients. However, two SNPs at FcεR1β E237G and FcεR1γ -237A>G were associated with atopy in AICU patients but not in ATCU. AICU patients with the AG/GG genotype of FcεR1β E237G and FcεR1γ -237G allele had a significantly higher frequency of atopy than those with the AA genotype (p = 0.02 and p = 0.040), respectively. The release of histamine from basophils induced by anti-IgE antibodies was significantly higher in AICU patients than in NCs and was increased in atopic patients compared with nonatopic patients (p = 0.006 and p = 0.007, respectively). The FcεR1β E237G and FcεR1γ -237T>G polymorphisms may be associated with the rate of atopy, which in turn could increase the release of histamine from basophils and may lead to the development of the AICU phenotype.