Clinical and genetic risk factors of self-reported penicillin allergy

Background

Patients with self-reported penicillin allergy are frequently denied β-lactam antibiotics.

Objective

To identify and correlate clinical and genetic risk factors of self-reported penicillin allergy.

Methods

We conducted a case-control study of adults recruited from allergists' offices. Cases had a history of urticaria, angioedema, wheeze, hypotension, vomiting, or anaphylaxis after a dose of penicillin. DNA from buccal swabs was genotyped for variants associated with candidate genes linked to immediate hypersensitivity (IL4, IL4R, and IL10) and penicillin metabolism (LACTB). Logistic regression was used to calculate the association between penicillin allergy and clinical and genetic factors.

Results

Seventeen allergists identified 76 adults. Complete data were available for 23 cases and 39 controls. Penicillin allergy was associated with a history of penicillin allergy in first-degree relatives (P = .002), a history of other adverse drug reactions (P = .008), and atopy (P = .039). However, in the multivariable analysis, only family history of penicillin allergy remained significant. IL4 single nucleotide polymorphisms (SNPs) rs11740584 (P = .012), rs10062446 (P = .021), and rs2070874 (P = .035) were associated and LACTB SNP rs2729835 (P = .058) was marginally associated with penicillin allergy. Adding rs11740584 or rs10062446 individually improved the clinical multivariable model (R² increased from 0.23 to 0.33). Haplotype analysis did not provide additional information to the SNP analysis.

Conclusion

Self-reported penicillin allergy may be influenced by clinical and genetic factors such as IL4.

Key words: Penicillin, drug allergy, adverse drug reaction, immediate hypersensitivity, genetics, IL-4

Abbreviations used: HWE, Hardy-Weinberg equilibrium, IL4R, IL-4 receptor gene, LACTB, β-Lactamase gene, LD, Linkage disequilibrium, OR, Odds ratio, SNP, Single nucleotide polymorphism, WGA, Whole genome amplification