RESUMEN
BACKGROUND: Interleukin (IL)-1 alpha and its receptor antagonist IL-1 ra play a role in skin inflammation. Several polymorphisms in the IL1 gene cluster, coding for IL-1 alpha, IL-1 ra, and IL-1 beta, influence their protein expression. Within this cluster, strong linkage disequilibrium has been shown. OBJECTIVE: We studied the association between the polymorphisms IL1A-889 (C-->T) and IL1B-31 (T-->C) and the concentration of IL-1 alpha and IL-1 ra in the stratum corneum (SC). METHOD: In 124 patients with chronic irritant contact dermatitis, we genotyped the IL1A-889 and IL1B-31 polymorphisms and determined the amount of IL-1 alpha and IL-1 ra on tape strips obtained from uninvolved skin of the volar forearm. RESULTS: The SC IL-1 alpha concentration was 23% and 47% lower in subjects with IL1A-889 C/T genotype and T/T genotype, respectively, compared with wild-type genotype. In subjects with IL1B-31 C/C genotype, the IL-1 alpha concentration was 51% lower compared with C/T and T/T genotypes. The ratio IL-1 ra/IL-1 alpha increased twofold in IL1A-889 C/T genotype and threefold in T/T genotype compared with wild type. CONCLUSIONS: We have shown a clear effect of IL1 genotype on protein expression in the SC. This altered expression may be responsible for the interindividual differences in the inflammatory response of the skin.
Asunto(s)
Dermatitis Irritante/genética , Epidermis/metabolismo , Proteína Antagonista del Receptor de Interleucina 1/metabolismo , Interleucina-1alfa/genética , Interleucina-1beta/genética , Polimorfismo de Nucleótido Simple , Adulto , Alelos , Análisis de Varianza , Enfermedad Crónica , ADN/análisis , Dermatitis Irritante/inmunología , Dermatitis Irritante/metabolismo , Femenino , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Proteína Antagonista del Receptor de Interleucina 1/genética , Interleucina-1alfa/metabolismo , Interleucina-1beta/metabolismo , Desequilibrio de Ligamiento , Masculino , Persona de Mediana Edad , Reacción en Cadena de la PolimerasaRESUMEN
BACKGROUND: Cytokines play an important role in skin inflammation. OBJECTIVES: We determined whether polymorphisms in cytokine genes contribute to the occurrence of occupational chronic irritant contact dermatitis (CICD). METHODS: In a case-control study, 9 polymorphisms in the genes coding for interleukin (IL)-1 alpha, IL-1 beta, IL-8, IL-10, and tumour necrosis factor (TNF)-alpha were determined in 197 patients with CICD. 217 apprentices in vocational training for high-risk occupations for CICD served as controls. RESULTS: For all polymorphisms, no differences in genotype distributions were found between patients and controls. However, in patients with self-reported low levels of wet work and irritant exposure, more TNFA -308 variant genotypes (G/A and A/A) were present compared with those exposed to higher levels or controls, which indicates a TNFA-induced increase of susceptibility. In patients with TNFA -308 variant genotypes, the prevalence of flexural eczema was higher (48% and 57%) compared with that in patients presented with wild-type genotype (30%). Regarding IL1A -889, prevalence of symptoms of dermatitis was lower in apprentices with T/T or C/T genotype (32% and 36%) compared with wild-type genotype (54%, C/C). This indicates a protective effect of these variant alleles in acquiring hand dermatitis. CONCLUSIONS: This study provides evidence that some genetic variations alter susceptibility to (chronic) dermatitis. Knowledge of the impact of genetic differences on the risk of CICD is essential in predictive testing of individuals at risk.