Résumé
Background: Allergic reactions to beta-lactam antibiotics represent the most frequent cause of immunological drug reactions.
Objective: This study evaluates the involvement of genetic susceptibility factors in patients with immediate allergic reactions to beta-lactams. We examined 15 single nucleotide polymorphisms (SNP) of genes coding proteins implicated in immunoglobulin (Ig)E synthesis regulation.
Methods: We performed a case-control study involving 44 patients with immediate beta-lactam allergy and 44 control subjects, all matched for sex and atopy. Interleukin (IL)-4, IL-13, IL-4R alpha, signal transducer and activator of transcription 6 (STAT6), interferon (IFN)-gamma R1, IFN-gamma R2 and Fc epsilon RI beta 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.
Results: 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 beta-lactam allergy in women and the Ile75Val variant of IL-4R alpha 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-4R alpha Ile75Val variant could have a paradoxal protective effect in atopic male patients (P = 0.004, OR = 0.07, CI: 0.01-0.66).
Conclusion: Our findings suggest that polymorphisms in the IL-10 promoter and IL-4R alpha genes are genetic factors that favour beta-lactam immediate allergies in female patients with atopy.