RELATION BETWEEN GLUCOCORTICOID RESISTANCE AND GLUCOCORTICOID RECEPTOR GENE BclI-POLYMORPHISM AND SOME CYTOKINE PROFILE PARAMETERS IN PATIENTS WITH HAND ECZEMA

Abstract

Though glucocorticoids are widely used in dermatological practice, some patients with hand eczema may have resistance to glucocorticoids, even when they are taken in heavy doses. Glucocorticoids mediate their actions through glucocorticoid receptors. Polymorphism of the glucocorticoid receptor gene (NR3C1) can inhibit the cellular response to glucocorticoids and lead to reduced response to the therapy. Some cytokines can affect the production of various glucocorticoid receptor subunits, modulating the cell response to glucocorticoids. However, there is still need in detailed study of pathogenetic mechanisms and the detection of highly specific predictors of glucocorticoid resistance. The aim of this work was to investigate the possible relation between glucocorticoid resistance in patients with hand eczema, rs41423247 SNP, and blood concentration of interleukin-17A and interleukin-2. The venous blood of 143 patients with hand eczema (42% of women and 58% of men) mean age 42.2 ± 11.1 years was taken for the study. During the patients examination the data on age, sex, body mass index (kg/m2), body mass index ≥ 25 (kg/m2(%)), the habit of smoking, concemtration of immunoglobulin E (iu/ml), interleukin-17A (pg/ml) and interleukin-2 (pg/ml) were obtained. The еczema аrea and severity index was assessed in each subject before the therapy and in two weeks since the therapy started. According to index value, all the patients were divided into three subgroups: mild eczema, moderate eczema, and severe eczema. Patients with mild and moderate eczema were prescribed to apply topical glucocorticoid 0.1% mometasone furoate cream twice a day for 2 weeks. The patients with severe hand eczema were prescribed to receive additional systemic corticosteroid, a solution of dexamethasone by intramuscular injection in a dose of 8 mg / day, then 4 mg / day for another 2 days. BclI SNP (rs41423247) of the glucocorticoid receptor gene (NR3C1) was determined using PCR-RFLP method. The quantitative variables were tested for normal distribution by the Shapiro-Wilk test. The comparisons of the means between the two subgroups were performed by Student's t-test for independent samples. The comparison of the frequencies distribution in the subgroups was calculated by using the Pearson test. The P value < 0.05 was considered as significant. Thus, the obtained results revealed that insensitivity to glucocorticoids in patients with hand eczema is related to NR3C1 gene Bcl-1 polymorphism, eczema severity and plasma level of interleukin-17, interleukin-2. The plasma content of interleukin-17 and interleukin-2 in patients with glucocorticoid resistance was significantly higher compared to hormone-sensitive subjects. There were significantly more people with the C/G- and G/G genotypes in the group that did not have a clinical response to therapy.