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

Authors
Kim, SH; Lee, JE; Jee, YK; Kim, YK; Park, HS; Min, KU; Park, HW; Adverse Drug Reaction Research Group in Korea
Citation
Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology, 39(12):1852-1856, 2009
Journal Title
Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology
ISSN
0954-78941365-2222
Abstract
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.
MeSH terms
AdolescentAdultAllelesAnti-Bacterial Agents/adverse effectsAnti-Bacterial Agents/immunology*Antigens, CD/geneticsAntigens, CD28/geneticsAntigens, CD40/genetics*Antigens, CD86/geneticsCD40 Ligand/genetics*Drug Eruptions/genetics*Drug Eruptions/immunology*FemaleGenetic Association StudiesGenotypeHumansInterleukin-1beta/geneticsKoreaMaleMiddle AgedPolymorphism, Single Nucleotide/geneticsPolymorphism, Single Nucleotide/immunologyTumor Necrosis Factor-alpha/geneticsYoung Adult
DOI
10.1111/j.1365-2222.2009.03336.x
PMID
19735272
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Allergy
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