Allelic variants of CD40 and CD40L genes interact to promote antibiotic-induced cutaneous allergic reactions


H-W Park, Department of Internal Medicine, Seoul National University, 28 Yongondong, Chongno-gu, Seoul 110-744, Korea.


Background The danger hypothesis provides a new perspective of the mechanisms underlying drug allergy. In this study, we evaluated associations between variations in the genes involved in danger signal pathways and antibiotic-induced cutaneous allergic reactions (AICARs).

Methods Two hundred cases with urticaria, angio-oedema, maculopapular rash, and erythema multiforme caused by antibiotics were extracted from the database of the Adverse Drug Reaction Research Group in Korea. All cases were confirmed by an allergy specialist. Causative antibiotics included penicillin, cephalosporin, quinolone, and others (approximately 40 different types). Ten single nucleotide polymorphisms (SNPs) in seven genes (−318C>T, +49A>G, and +6230G>A in CTLA4, IVS+17T>C in CD28, −3479T>G and I170V in CD86, −1C>T in CD40, −3458A>G in CD40LG, −308G>A in TNF, and −31T>C in IL1B) were scored for cases and for healthy subjects without a history of AICARs.

Results Our analysis failed to reveal differences in the distribution of the 10 SNPs between cases and controls. However, we could find a gene–gene interaction between −1C>T in CD40 and −3458A>G in CD40L using multifactor dimensionality reduction analysis. Subjects with minor alleles of both SNPs showed a significant risk for developing AICARs [P=0.017, odds ratio (OR) (95% confidence interval)=2.93 (1.20–7.97)].

Conclusion Our findings suggest that a genetic interaction between CD40 and CD40L favours the development of AICARs.