Pharmacogenetic basis for severe asthma exacerbations
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* Shoaib Faruqi

Activation of CD23, a low affinity IgE receptor, results in downregulation of IgE-mediated immune responses. CD23 is encoded for by the Fc fragment of IgE low affinity II receptor (FCER2) gene. IgE levels may increase in children with asthma treated with inhaled corticosteroids, and this may be explained by a decrease in FCER2 expression by corticosteroids. Also, elevated IgE levels are associated with an increased risk of severe exacerbations of asthma. This study investigates whether single nucleotide polymorphisms (SNPs) in FCER2 are associated with increased severe exacerbations in patients with asthma on inhaled corticosteroids.

Three hundred and eleven children randomised to inhaled budesonide and followed up over a period of 4 years as part of the Childhood Asthma Management Program were included in the study. SNPs were identified from resequencing FCER2 genomic fragments. The primary outcome was “severe exacerbations”, which comprised either an emergency department visit or hospitalisation for asthma. Associations between FCER2 status and 4-year log IgE levels and severe exacerbations were analysed. Subsequent confirmatory analyses of the main effects of a novel common SNP, T2206C, were analysed in white and African American subgroups. Baseline IgE levels were associated with severe exacerbations. Variations in SNPs, including T2206C, were significantly associated with increased IgE levels. The SNPs associated with increased IgE were associated with an increased risk of severe exacerbations. There was a markedly increased tendency for severe exacerbations in both white and African American subjects homozygous for the mutant T2206C allele. This association was not seen in subjects not on inhaled corticosteroids.

This interesting study suggests a possible pharmacogenetic predictor of severe exacerbations in asthma. However, the specific nature of the subject group prevents generalisation.

Tantisira KG, Silverman ES, Mariani TJ, *et al*. FCER2: a pharmacogenetic basis for severe exacerbations in children with asthma. *J Allergy Clin Immunol* 2007;**120**:1285–91