Gene-gene interactions of IL13 and IL4RA variants in immediate allergic reactions to betalactam antibiotics

OBJECTIVES: Immediate reactions - particularly anaphylactic ones - to betalactams are the most common adverse reactions to antibiotics mediated by a specific immunologic mechanism. The genetic risk factors influencing these mechanisms are poorly known. We aimed to evaluate the association between immediate allergic reactions to betalactams and the polymorphisms of IL13 (R130Q and -1055C>T variants) and IL4RA (I50V, S478P, and Q551R variants). METHODS: We determined these gene variants in 210 patients and 265 age-paired and gender-paired control subjects from Italy. RESULTS: The combination of the less frequent allele of the IL13 R130Q polymorphism with any of the predominant homozygous genotypes of the three polymorphisms of IL4RA was more significantly associated with the risk of betalactam allergy (P=0.0006, 0.0077, and 0.0041, respectively) than any polymorphism considered alone (P=0.1745, 0.0268, 0.1812, 0.0152, respectively). The same associations were observed with serum IgE levels (IL13/IL4RA variant combinations: P=0.0009, 0.0007, 0.0020, respectively and each variant: P=0.0201, 0.0021, 0.0531, and 0.0417, respectively). The combination of IL4RA variants with -1055 C>T polymorphism produced similar associations. CONCLUSION: Our data suggest that these combinations of IL13 and IL4RA variants are predictors of immediate allergic reactions to betalactams through a mechanism related to IgE production.