Association Study of the Chromosomal Region Containing the FCER2 Gene Suggests It Has a Regulatory Role in Atopic Disorders

Abstract

On the basis of studies with animal models, the gene for the low-affinity receptor for immunoglobulin E (IgE) (FCER2, CD23) has been implicated as a candidate for IgE-mediated allergic diseases and bronchial hyperreactivity, or related traits. Given evidence for genetic complexity in atopic disorders, we sought to study two European subpopulations, Finnish and Catalonian. We studied three phenotypic markers: (1) total serum IgE level; (2) asthma; and (3) specific IgE level for a mixture of the most common aeroallergens in Finland. Altogether, eight polymorphic markers spanning a region of 10 cM around the FCER2 gene on chromosome 19p13 were analyzed in 124 families. The physical order of the markers and the location of the FCER2 gene were confirmed by using radiation hybrids. The allele and haplotype association study showed a suggestive haplotype association (significance of p </= 0.03 based on a permutation test) for a high serum IgE response. In a subset of chromosomes segregating with asthma in families with two or more affected members, a single haplotype was found to be highly enriched (p = 8.3 x 10(-6)). However, sequence polymorphisms, which would verify structural differences in the FCER2 gene, were not detected in the coding region of the receptor. Our results suggest that chromosome 19p13 might harbor a genetic determinant of IgE-related traits. Studies in other population samples are needed to verify this finding.

FCER2: A pharmacogenetic basis for severe exacerbations in children with asthma

“…This expands on a previous study that noted a haplotypic association of microsatellite variants in and around FCER2 with elevations in IgE levels. 35 The effect of FCER2 genetic variation on increasing IgE levels may be further augmented by the decreases in CD23 expression associated with corticosteroid administration. [19][20][21][22] We have substantiated this by noting that the highest IgE levels were found in subjects both homozygous for the T2206C variant and taking ICSs, including the demonstration of a significant steroid-genotype interaction in white subjects.…”

Association analysis of common variants of STAT6, GATA3, and STAT4 to asthma and high serum IgE phenotypes

“…The details of the recruitment and diagnostic testing have been described previously. 31,32 Phenotypes available for this cohort (average age, 43 years; 37 years among individuals with high and 45 years among individuals with low serum IgE) were asthma status, serum total IgE level (Diagnostics CAP FEIA), and blood eosinophil level. Among the genotyped samples there were no non-atopic individuals with high IgE values.…”

Polymorphism R62W results in resistance of CD23 to enzymatic cleavage in cultured cells

“…A significant allele and haplotype association of CD23 with the phenotypes in allergic diseases has been observed in a genetic epidemiological study. 20 CD23 single nucleotide polymorphisms (SNPs) have recently been associated with a significantly increased severe exacerbation in children with asthma by Tantisira et al 21 Given that CD23 can mediate allergen presentation through IgE, it was hypothesized that the SNPs of CD23 may impact allergen-induced T-cell responses, possibly accounting for some associations of CD23 genetic polymorphisms with allergic diseases. In an epidemiological study, we recruited 42 human subjects, including 22 with allergy or asthma and 20 as healthy controls.…”