Sequence variants in the FcepsilonRI alpha chain gene.

There is a relationship between IgE levels and expression of high-affinity IgE receptors (FcepsilonRI). Because the alpha chain is the only portion of the receptor that binds directly to IgE, we reasoned that sequence variants in the FcepsilonRI alpha gene may exist that alter these binding events. We screened all of the exons and the promoter region of the FcepsilonRI alpha chain gene with genomic DNA from 389 asthmatic and 341 normal control subjects for mutations by using single-stranded conformational polymorphism analysis. No nonsynonomous single nucleotide polymorphisms (SNPs) were identified in the coding region. Three SNPs were found in the promoter region: an A/C transversion at -770 from the translation start site; a G/A transition at -664; and a T/C transition at -335. No differences in allele frequencies were detected between asthmatic subjects and controls. Homozygosity for the C variant at locus -335 was more common in Caucasian asthmatic patients with IgE levels in the lower quartile than in the upper quartile (P = 0.032). An analysis of highly polymorphic SNPs indicated that this association is unlikely to be due to population substructure. We conclude that homozygosity for the C allele of FcepsilonRI alpha chain variant is associated with lower IgE levels.