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J Appl Physiol (February 15, 2002). doi:10.1152/japplphysiol.00993.2001
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Articles in PresS, published online ahead of print February 15, 2002
J Appl Physiol, 10.1152/jap.00993.2001
Submitted on September 28, 2001
Accepted on January 29, 2002

Sequence Variants in the Fc{epsilon}RI Alpha Chain Gene

Toshiki Shikanai1, Eric S Silverman2, Brian W Morse2, Craig M Lilly2, Hiroshi Inoue1, and Jeffrey M Drazen2*

1 Division of Pulmonary Medicine, Iwate Medical University, Morioka, Iwate, Japan
2 Division of Pulmonary Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA

* To whom correspondence should be addressed. E-mail: jdrazen{at}nejm.org.

There is a relationship between IgE levels and expression of high-affinity IgE receptors (Fc{epsilon}RI). Since the alpha chain is the only portion of the receptor that binds directly to IgE, we reasoned that sequence variants in the Fc{epsilon}RI alpha gene may exist that alter these binding events. We screened all the exons and the promoter region of the Fc{epsilon}RI alpha chain gene with genomic DNA from 389 asthmatics and 341 normal control subjects for mutations using single-stranded conformational polymorphism (SSCP) analysis. No non-synonomous single nucleotide polymorphisms (SNPs) were identified in the coding region. Three SNPs were found in the promoter region: an A to C transversion at -770 from the translation start site; a G to A transition at -664; and a T to C transition at -335. No differences in allele frequencies were detected between asthmatics and controls. Homozygosity for the C variant at locus -335 was more common in Caucasian asthmatics 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 Fc{epsilon}RI {alpha} chain variant is associated with lower IgE levels.




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