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Association between Bcl I polymorphism in the NR3C1 gene and in vitro individual variations in lymphocyte responses to methylprednisolone
Author(s) -
Cuzzoni Eva,
De Iudicibus Sara,
Bartoli Fiora,
Ventura Alessandro,
Decorti Giuliana
Publication year - 2012
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.2011.04130.x
Subject(s) - methylprednisolone , glucocorticoid , peripheral blood mononuclear cell , glucocorticoid receptor , in vitro , biology , immunology , lymphocyte , genotype , pharmacogenetics , medicine , pharmacology , gene , genetics
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • In vitro lymphocyte steroid sensitivity has been suggested as a useful tool to predict in vivo response to glucocorticoid treatment in different inflammatory chronic diseases. • A correlation between genetic polymorphisms and clinical response to glucocorticoids has been demonstrated in these patients. WHAT THIS STUDY ADDS • The Bcl I polymorphism in the glucocorticoid receptor ( NR3C1 ) gene is associated with higher methylprednisolone potency in vitro. • The combined evaluation of the in vitro sensitivity to methylprednisolone and Bcl I polymorphism could represent an aid for physicians to adjust therapy a priori . AIM To evaluate the association between the in vitro sensitivity of peripheral blood mononuclear cells (PBMCs) to methylprednisolone (MP) and the presence of genetic polymorphisms involved in glucocorticoid (GC) response. METHODS In vitro MP inhibition of the proliferation of lymphocytes stimulated with concanavalin A was determined. Non linear regression of dose–response data was performed computing the MP concentration required to reduce proliferation to 50% (I C 50 ). The maximum inhibition achievable at the highest MP concentration (I max ) was also calculated. Moreover, the Taqman technique was used to analyze the Bcl I polymorphism in the NR3C1 gene and the Leu155His polymorphism in the NALP1 gene. RESULTS A significant association between the Bcl I mutated genotype and an increased in vitro sensitivity to GCs was observed. CONCLUSIONS The a priori evaluation of the Bcl I polymorphism, associated with a lymphocyte proliferation assay, could represent a useful diagnostic tool for the optimization of steroid treatment.