Comparison of cytokine gene polymorphism in drug-induced maculopapular eruption, urticaria and drug reaction with eosinophilia and systemic symptoms ( DRESS).

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), IL1-beta-511C>T (rs 16944), IL1- RN intron-2- VNTR (rs2234663), IL2-330T>G (rs 2069762), IL4-33C>T (rs 2070874), IL5-745C>T (rs 2069812), IL10-592C>A (rs 1800872), IL16-295T>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 IL1- RN-A2 and IL1-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 IL10-592A 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 IL1-cluster polymorphisms and haplotypes and the IL10-592A allele (a low IL10 producer) are associated with DRESS. These gene variants may decrease drug tolerance and promote herpes virus reactivation. [ABSTRACT FROM AUTHOR]