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J Appl Physiol 93: 37-41, 2002. First published February 15, 2002; doi:10.1152/japplphysiol.00993.2001
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Vol. 93, Issue 1, 37-41, July 2002

Sequence variants in the Fcepsilon RI alpha chain gene

Toshiki Shikanai1, Eric S. Silverman1, Brian W. Morse1, Craig M. Lilly1, Hiroshi Inoue2, and Jeffrey M. Drazen1

1 Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115; and 2 Iwate Medical University, Morioka, Iwate 020-8505, Japan

There is a relationship between IgE levels and expression of high-affinity IgE receptors (Fcepsilon RI). Because the alpha chain is the only portion of the receptor that binds directly to IgE, we reasoned that sequence variants in the Fcepsilon RI alpha gene may exist that alter these binding events. We screened all of the exons and the promoter region of the Fcepsilon RI 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 Fcepsilon RI alpha chain variant is associated with lower IgE levels.

asthma; atopy; immunoglobulin E; polymorphism; association study; genetics; allergy


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