Association study of the chromosomal region containing the FCER2 gene suggests it has a regulatory role in atopic disorders

On the basis of studies with animal models, the gene for the low-affinity receptor Per 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 (signficance of p less than or equal to 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.