TY - JOUR
T1 - Glucocorticoid resistance in Crohn's disease and ulcerative colitis
T2 - An association study investigating GR and FKBP5 gene polymorphisms
AU - Maltese, P.
AU - Palma, L.
AU - Sfara, C.
AU - De Rocco, P.
AU - Latiano, A.
AU - Palmieri, O.
AU - Corritore, G.
AU - Annese, V.
AU - Magnani, M.
PY - 2012/10
Y1 - 2012/10
N2 - 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.
AB - 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.
KW - FKBP5
KW - glucocorticoid receptor
KW - glucocorticoid therapy
KW - inflammatory bowel disease
KW - single-nucleotide polymorphisms
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U2 - 10.1038/tpj.2011.26
DO - 10.1038/tpj.2011.26
M3 - Article
C2 - 21788965
AN - SCOPUS:84866738606
VL - 12
SP - 432
EP - 438
JO - Pharmacogenomics Journal
JF - Pharmacogenomics Journal
SN - 1470-269X
IS - 5
ER -