Department of Biomolecular Sciences, University of Urbino, Urbino, Italy.
Pharmacogenomics J. 2012 Oct;12(5):432-8. doi: 10.1038/tpj.2011.26. Epub 2011 Jul 26.
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.
本研究旨在探讨糖皮质激素受体（GR）和相关共伴侣 FKBP5 基因单核苷酸多态性（SNPs）在克罗恩病（CD）和溃疡性结肠炎（UC）患者糖皮质激素（GC）耐药中的作用。我们开发了一种高分辨率 DNA 熔解方法，可同时鉴定 GR（BclI、N363S 和 ER22/23EK）和 FKBP5（rs3800373、rs1360780 和 rs4713916）多态性。在接受 GC 治疗的 100 例连续 CD 和 100 例 UC 患者（50 例应答者和 50 例抵抗者）中确定了基因型频率。FKBP5 多态性 rs4713916（G/A）在 FKBP5 假定启动子区域的变异与 CD 患者对 GC 治疗的抵抗显著相关（应答者=17%，抵抗者=35%；P=0.0043）。在 UC 患者中未发现显著差异。如果这些初步发现得到证实，GR 和 FKBP5 突变分析的组合可能有助于识别 CD 患者中更有可能从 GC 治疗中获益的亚组。
