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Glucocorticoid resistance in Crohn's disease and ulcerative colitis: an association study investigating GR and FKBP5 gene polymorphisms

The Pharmacogenomics Journal volume 12, pages 432–438 (2012)Cite this article

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Abstract

The aim of this study is to investigate the role of single-nucleotide polymorphisms (SNPs) of the glucocorticoid receptor (GR) and of the related co-chaperone FKBP5 genes in the development of glucocorticoid (GC) resistance in Crohn's disease (CD) and ulcerative colitis (UC) patients. We have developed a high-resolution DNA melting method that allows simultaneous identification of GR (BclI, N363S and ER22/23EK) and FKBP5 (rs3800373, rs1360780 and rs4713916) polymorphisms. Genotype frequencies were determined in 100 consecutive CD and 100 UC patients under GCs therapy (50 responders and 50 resisters). The variation of FKBP5 polymorphism rs4713916 (G/A), in the putative promoter region of FKBP5, is significantly associated with resistance to GC treatment in CD (responder=17% versus resister=35%; P=0.0043). No significant differences were found in UC patients. If these preliminary findings will be confirmed, the combination of GR and FKBP5 mutational analyses could help to identify subgroups of CD patients with higher chances to benefit from GC treatment.

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Acknowledgements

We thank the patients affected by IBD recruited at IRCCS-‘Casa Sollievo della Sofferenza’ Hospital in San Giovanni Rotondo, Italy, whose altruism and trust in biomedical research have made this study possible. No writing assistance was used in the production of this manuscript. This study was supported by the RC1002GA25 funding from the Italian Minister of Health, granted to the IRCCS-‘Casa Sollievo della Sofferenza’ Hospital; and by PRIN-MIUR funding, granted to the Department of Biomolecular Sciences, University of Urbino.

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Author notes

  1. P Maltese and L Palma: These authors contributed equally to this study.

Authors and Affiliations

  1. Department of Biomolecular Sciences, University of Urbino, Urbino, Italy

    P Maltese, L Palma, C Sfara, P de Rocco & M Magnani

  2. Unit of Gastroenterology, IRCCS ‘Casa Sollievo della Sofferenza’, Hospital San Giovanni Rotondo, Italy

    A Latiano, O Palmieri & G Corritore

  3. Gastroenterology Unit, AOU Careggi Hospital, Florence, Italy

    V Annese

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  1. P Maltese
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  2. L Palma
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  3. C Sfara
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  4. P de Rocco
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Correspondence to M Magnani.

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Maltese, P., Palma, L., Sfara, C. et al. Glucocorticoid resistance in Crohn's disease and ulcerative colitis: an association study investigating GR and FKBP5 gene polymorphisms. Pharmacogenomics J 12, 432–438 (2012). https://doi.org/10.1038/tpj.2011.26

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