Genetic factors modifying response to glucocorticoid treatment in chronic pediatric inflammatory bowel diseases

Abstract


The article concerns genetic factors that determine efficiency of steroid treatment for chronic inflammatory bowel diseases (IBD) in children, focused, mostly, on Crohn disease and nonspecific ulcerative colitis. Their incidence comprises 5 to 15 per 100 000 children and adolescents. In acute phase, therapy of these diseases is based on salicylates and glucocorticoids which regulate cytokine network and immune cell functions. Application of high-dose glucocorticoids (GCs) exerts а sufficient immunosuppressive action. These effects are performed via specific GC receptors in the target cell populations. Hence, numbers and functionality of GC receptors are important for clinical response to GC treatment. The aim of this review is discern major genetic effects upon functioning of glucocorticoid receptors. Here we discuss effects of N363S, ER22/23EK, and NR3C1 variants, the most known GC functional gene polymorphisms. These gene variants are often associated with altered GC gene expression in individual cases of IBD. Moreover, some other gene variants are able to modulate the GC receptor expression, thus making it difficult to assess genetic predisposition to altered clinical response to glucocorticoids. Hence, the regulatory effects of single gene variants upon GC receptors may not show direct correlations with clinical effects of the drug. Therefore, we propose an immediate way to assess the gene activity, i. e., quantitative analysis of the gene transcription (mRNA detection) in the patients’ cells before and during glucocorticoid therapy, presuming further application of this parameter as a predictive marker for evaluation of optimal therapeutic response in the individual IBD patients.

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About the authors

Nadezhda Konstantinovna Zaletova

St. Petersburg State Pediatric Medical University

Email: nadezhda-zaletova@yandex.ru
Postgraduate Student

Lubov Pavlovna Vostokova

St. Petersburg State Pediatric Medical University

Email: vostokova50@mail.ru
Research Associate, Laboratory of Molecular Diagnostics with a group for Ecogenetics, Research Center

Alexey Borisovich Chukhlovin

St. Petersburg State Pediatric Medical University

Email: alexei.chukh@mail.ru
PhD, MD, Dr Med Sci, Head, Laboratory of Molecular Diagnostics with extended Group for Ecogenetics

Elena Alexandrovna Kornienko

St. Petersburg State Pediatric Medical University

Email: elenkornienk@yandex.ru
PhD, MD, Professor, Head, Department of Gastroenterology

Anna Timofeevna Tretjak

St. Petersburg State Pediatric Medical University

Email: a.t.tretiak@gmail.com
Research Associate, Laboratory of Molecular Diagnostics with a group for Ecogenetics, Research Center

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Copyright (c) 2015 Zaletova N.K., Vostokova L.P., Chukhlovin A.B., Kornienko E.A., Tretjak A.T.

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