FUNCTIONAL-ANALYSIS OF HISTAMINE-RELEASE FROM BASOPHILS AND MAST-CELLS IN SUBJECTS WITH THE ILE-181-]LEU VARIANT OF FC-EPSILON-RI-BETA

1. Atopy is a genetically heterogeneous disorder, but there is now str ong evidence that one important locus is on chromosome 11q13, Fc epsil on RI-beta at that location has been identified as a candidate gene an d variants have been associated with atopy in population studies. 2. N o information is available on the functional consequences of any of th ese variants, and defining this may prove difficult because of the com plexity of the atopy phenotype and because Fc epsilon RI beta is expre ssed 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 hista mine release in nine atopic individuals with Ile-181-->Leu mutation of Fc epsilon RI beta, and ten unrelated similarly atopic individuals wi thout Ile-181-->Leu mutation, There were non-significant trends for Il e-181-->Leu-positive atopic subjects to produce wheal responses at low er allergen challenge in skin prick tests, and to release more histami ne from basophils following in vitro allergen challenge. 4. The data d o not provide decisive evidence of functional differences between atop ic subjects with Ile-181-->Leu and other atopic individuals; more disc riminating functional experiments are required.