Original article: IL-10 promoter and IL4-R[alpha] gene SNPs are associated with immediate [beta]-lactam allergy in atopic women

Allergic reactions to β -lactam antibiotics represent the most frequent cause of immunological drug reactions. This study evaluates the involvement of genetic susceptibility factors in patients with immediate allergic reactions to β -lactams. We examined 15 single nucleotide polymorphisms (SNP) of genes coding proteins implicated in immunoglobulin (Ig)E synthesis regulation. We performed a case-control study involving 44 patients with immediate β -lactam allergy and 44 control subjects, all matched for sex and atopy. Interleukin (IL)-4, IL-13, IL-4Rα , signal transducer and activator of transcription 6 (STAT6), interferon (IFN)-γ R1, IFN-γ R2 and Fc[varepsilon]RIβ gene polymorphisms were determined using polymerase chain reaction (PCR) restriction fragment length polymorphism, and IL-21R gene and IL-10 promoter polymorphisms by direct sequencing. Our analysis did not reveal differences in the distribution of the 15 SNPs between allergic patients and controls. However, among atopic subjects, we found two distinct significant associations between immediate β -lactam allergy in women and the Ile75Val variant of IL-4Rα gene (P = 0.012, OR = 5.4, CI: 1.16-27.7), and two linked IL-10 promoter gene polymorphisms, -819C>T and -592 C>A (P = 0.023, OR = 17.5, CI: 1.26-533.07). In contrast, we observed no association in allergic male subjects in the atopic population. Interestingly, the IL-4Rα Ile75Val variant could have a paradoxal protective effect in atopic male patients (P = 0.004, OR = 0.07, CI: 0.01-0.66). Our findings suggest that polymorphisms in the IL-10 promoter and IL-4Rα genes are genetic factors that favour β -lactam immediate allergies in female patients with atopy.