1. Atopy is a genetically heterogeneous disorder, but there is now strong evidence that one important locus is on chromosome 11q13. FcεRI-β at that location has been identified as a candidate gene and variants have been associated with atopy in population studies.
2. No information is available on the functional consequences of any of these variants, and defining this may prove difficult because of the complexity of the atopy phenotype and because FcεRIβ is expressed on a range of cells with different functions, including basophils, mast cells, eosinophils and antigen-presenting Langerhan's cells.
3. We have conducted a qualitative study of mast cell and basophil histamine release in nine atopic individuals with Ile-181→Leu mutation of FcεRIβ, and ten unrelated similarly atopic individuals without Ile-181→Leu mutation. There were non-significant trends for Ile-181→Leu-positive atopic subjects to produce wheal responses at lower allergen challenge in skin prick tests, and to release more histamine from basophils following in vitro allergen challenge.
4. The data do not provide decisive evidence of functional differences between atopic subjects with Ile-181→Leu and other atopic individuals; more discriminating functional experiments are required.