Glucocorticoid resistance in Crohn's disease and ulcerative colitis: an association study investigating GR and FKBP5 gene polymorphisms
Glucocorticoid resistance in Crohn's disease and ulcerative colitis: an association study investigating GR and FKBP5 gene polymorphisms
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DOI：
10.1038/tpj.2011.26
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发表时间：
2012-10-01
影响因子：
2.8
通讯作者：
Magnani, M.
中科院分区：
文献类型：
--
作者：
Maltese, P.;Palma, L.;Magnani, M.
本研究旨在探讨糖皮质激素受体(GR)单核苷酸多态(SNPs)及相关辅助伴侣基因FKBP5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。我们建立了一种高分辨率的DNA熔融方法，可以同时检测GR(BclI，N363S和ER22/23EK)和FKBP5(rs3800373，rs1360780和rs4713916)的多态性。对100例接受GCS治疗的连续CD和100例UC患者(50名应答者和50名抵抗者)进行了基因频率测定。FKBP5基因启动子区rs4713916(G/A)多态与CD对GC治疗的耐受性显著相关(响应者=17%，抵抗者=35%；P=0.0043)。UC患者与正常对照组比较差异无统计学意义。如果这些初步发现得到证实，GR和FKBP5突变分析的结合可能有助于识别CD患者亚群中更有机会从GC治疗中受益的人群。药物基因组学杂志(2012年)12432-438；doi：10.1038/tpj.2011.26；2011年7月26日在线发布
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. The Pharmacogenomics Journal (2012) 12, 432-438; doi:10.1038/tpj.2011.26; published online 26 July 2011