Analysis of high-affinity IgE receptor (FcepsilonR1) 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 FcepsilonR1beta and FcepsilonR1gamma in patients with CU including AICU and aspirin-tolerant CU (ATCU) by analyzing the genotypes and haplotypes of four subsets of FcepsilonR1 genes in association with various clinical parameters. Four polymorphisms of FcepsilonR1 (FcepsilonR1beta -109T>C, FcepsilonR1beta E237G, FcepsilonR1gamma -237A>G, and FcepsilonR1gamma -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 FcepsilonR1 single-nucleotide polymorphisms (SNPs; p > 0.05) in CU including AICU and ATCU patients. However, two SNPs at FcepsilonR1beta E237G and FcepsilonR1gamma -237A>G were associated with atopy in AICU patients but not in ATCU. AICU patients with the AG/GG genotype of FcepsilonR1beta E237G and FcepsilonR1gamma -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 FcepsilonR1beta E237G and FcepsilonR1gamma -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.