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

Cited 11 time in Web of Science Cited 12 time in Scopus
Authors
Kim, Sae-H; Lee, J-E; Kim, Sang-H; Jee, Y-K; Park, H-S; Park, H-W; Min, K-U; Kim, Y-K
Issue Date
2009-12
Publisher
WILEY-BLACKWELL PUBLISHING, INC
Citation
CLINICAL AND EXPERIMENTAL ALLERGY; Vol.39 12; 1852-1856
Keywords
antibioticsdrug hypersensitivityCD40CD40 ligand
Abstract
P>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. Cite this as: Sae-H Kim, J-E Lee, Sang-H Kim, Y-K Jee, Y-K Kim, H-S Park, K-U Min, H-W Park and The Adverse Drug Reaction Research Group in Korea, Clinical & Experimental Allergy, 2009 (39) 1852-1856.
ISSN
0954-7894
Language
English
URI
https://hdl.handle.net/10371/76318
DOI
https://doi.org/10.1111/j.1365-2222.2009.03336.x
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College of Medicine/School of Medicine (의과대학/대학원)Internal Medicine (내과학전공)Journal Papers (저널논문_내과학전공)
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