Association between BclI polymorphism in the NR3C1 gene and in vitro individual variations in lymphocyte responses to methylprednisolone.
BACKGROUND
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.


CONCLUSIONS
The BclI 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 BclI 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% (IC(50) ). The maximum inhibition achievable at the highest MP concentration (I(max) ) was also calculated. Moreover, the Taqman technique was used to analyze the BclI polymorphism in the NR3C1 gene and the Leu155His polymorphism in the NALP1 gene.


RESULTS
A significant association between the BclI mutated genotype and an increased in vitro sensitivity to GCs was observed.


CONCLUSIONS
The a priori evaluation of the BclI polymorphism, associated with a lymphocyte proliferation assay, could represent a useful diagnostic tool for the optimization of steroid treatment.
Department of Life Sciences Department of Medical, Surgical and Health Sciences, University of Trieste, Via L. Giorgieri 7/9, Trieste, Italy.
Eva
E
Cuzzoni
Sara
S
De Iudicibus
Fiora
F
Bartoli
Alessandro
A
Ventura
Giuliana
G
Decorti
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000293:Adolescent; D000328:Adult; D051017:Apoptosis Regulatory Proteins / Q000235:genetics; D019938:Cyclin D1 / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005838:Genotype; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects*; D008297:Male; D008775:Methylprednisolone / Q000494:pharmacology*; D008875:Middle Aged; D000070576:NLR Proteins; D020641:Polymorphism, Single Nucleotide; D011965:Receptors, Glucocorticoid / Q000235:genetics*; D055815:Young Adult
D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D005938:Glucocorticoids; D000070576:NLR Proteins; C427903:NLRP1 protein, human; C497713:NR3C1 protein, human; D011965:Receptors, Glucocorticoid; D019938:Cyclin D1; D008775:Methylprednisolone