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Comparison of cytokine gene polymorphism in drug‐induced maculopapular eruption, urticaria and drug reaction with eosinophilia and systemic symptoms ( DRESS )
Author(s) -
Barbaud A.,
Waton J.,
Herbeth B.,
Bursztejn A.C.,
Bollaert M.,
Schmutz J.L.,
GuéantRodriguez R.M.,
Namour F.,
Guéant J.L.,
AimoneGastin I.
Publication year - 2014
Publication title -
journal of the european academy of dermatology and venereology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.655
H-Index - 107
eISSN - 1468-3083
pISSN - 0926-9959
DOI - 10.1111/jdv.12130
Subject(s) - medicine , eosinophilia , odds ratio , toxic epidermal necrolysis , haplotype , gastroenterology , allele , polymorphism (computer science) , allele frequency , genetic predisposition , immunology , adverse drug reaction , drug , dermatology , pharmacology , gene , genetics , biology , disease
Background Polymorphisms of genes controlling cytokine production have not been studied in the genetic susceptibility to cutaneous adverse drug reactions ( CADR ). Objectives The objective was to determine whether polymorphisms in nine cytokine genes were associated to the occurrence of drug reaction with eosinophilia and systemic symptoms ( DRESS ) compared to drug‐induced maculopapular eruption or urticaria and to controls without drug intolerance. Methods Results from 118 patients with a well‐defined CADR were compared to 236 controls without drug intolerance living in the same area of France. We assessed nine polymorphisms: interleukin ( IL )1‐alpha‐889C>T (rs 1800587), IL 1‐beta‐511C>T (rs 16944), IL 1‐ RN intron‐2‐ VNTR (rs2234663), IL 2‐330T>G (rs 2069762), IL 4‐33C>T (rs 2070874), IL 5‐745C>T (rs 2069812), IL 10‐592C>A (rs 1800872), IL 16‐295T>C (rs 4778889) and tumour necrosis factor‐alpha‐308G>A (rs 1800629). Results Three polymorphisms exhibited a significant association with CADR ( P < 0.05). The combination of the IL 1‐ RN ‐A2 and IL 1‐beta‐511C alleles was statistically different between cases and controls ( P = 0.007) and the A2C haplotype was associated with susceptibility to CADR , particularly in drug reaction with eosinophilia and systemic symptoms ( DRESS ) patients (odds ratio = 3.22; 95% confidence interval = 1.23–8.41; P = 0.016). The frequency of the IL 10‐592A allele was higher in DRESS patients than in controls (dominant model CC vs. CA + AA : P = 0.035). These abnormalities were not evident in maculopapular eruptions or urticaria. Conclusions This is the first study showing that IL 1‐cluster polymorphisms and haplotypes and the IL 10‐592A allele (a low IL 10 producer) are associated with DRESS . These gene variants may decrease drug tolerance and promote herpes virus reactivation.