Shikanai T, Silverman ES, Morse BW, Lilly CM, Inoue H, Drazen JM. J Appl Physiol. 2002;93:37–41
Purpose of Study.
A known relationship exists between immunoglobulin E (IgE) levels and expression of high-affinity IgE receptors (FcεRI). Sequence variants in the IgE-binding alpha chain of FcεRI, which may affect IgE binding, were examined in asthmatic and nonasthmatic subjects to look for a relationship to IgE levels.
The study subjects were 389 patients with asthma treated only with inhaled albuterol and with an average forced expiratory volume in 1 second (FEV1) of 62.3% of predicted, and 341 patients without a history of asthma or atopy by questionnaire.
DNA was extracted from peripheral blood and screened for mutations in the core promoter and exons of the FcεRI alpha chain gene by single-strand conformational polymorphism using radiolabelled primers. The most common site of polymorphism, the T/C −335 locus, was genotyped by restriction fragment length polymorphism. For stratification analysis, subjects were genotyped at 40 unlinked candidate single nucleotide polymorphisms, selected from a database. IgE levels were measured for each subject. For subjects in the highest and lowest quartile of IgE, stratification analysis was performed to look for genetic polymorphisms occurring at high or low frequency.
Three single nucleotide polymorphisms were detected in the 5′ flanking region of the FcεRI alpha chain gene, although no variants were detected in the gene itself. The most common was a T/C translocation at −335 base-pairs before the translational start site, whose frequency differed significantly between whites and blacks (P < .0001). In the entire cohort of white asthmatic patients, the T/C translocation was not associated with IgE levels, but a lower proportion of the CC genotype was found in whites in the highest quartile of IgE. In black asthmatics, the same trend was not observed.
Homozygosity for the C allele at locus −335 of the IgE-binding alpha chain of FcεR1 may lead to lower IgE binding.
This study population may have been biased toward milder or undertreated asthmatics, because no patients on medications other than inhaled albuterol met the selection criteria. Although this study suggests a possible connection between IgE levels and T/C translocation at the −335 locus of the FcεRI alpha chain promoter region, the overall lack of association between the IgE level and CC genotype at this locus raises additional questions about the relationship of this translocation to IgE binding. Future studies including a more representative asthmatic population may show a clearer relationship between FcεRI promoter translocations and IgE binding.