Division of Gastroenterology and Hepatology, University of Colorado Denver, 12631 East 17th Avenue, MS B158, Aurora, CO 80045, USA.
F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars Sinai Medical Center, 8730 Alden Drive, Suite E235, Los Angeles, CA 90048, USA.
Nat Rev Gastroenterol Hepatol. 2014 May;11(5):287-99. doi: 10.1038/nrgastro.2013.242. Epub 2013 Dec 17.
The expanding knowledge of the role of genetic variants involved in the susceptibility to IBD heralds an era of disease categorization beyond Crohn's disease and ulcerative colitis. A more robust molecular definition of the spectrum of IBD subtypes is likely to be based on specific molecular pathways that determine not only disease susceptibility but also disease characteristics such as location, natural history and therapeutic response. Evolving diagnostic panels for IBD will include clinical variables and genetic markers as well as other indicators of gene function and interaction with environmental factors, such as the microbiome. Multimodal algorithms that combine clinical, serologic and genetic information are likely to be useful in predicting disease course. Variation in IBD-susceptibility and drug-related pathway genes seems to influence the response to anti-TNF therapy. Furthermore, gene expression signatures and composite models have both shown promise as predictors of therapeutic response. Ultimately, models based on combinations of genotype and gene expression data with clinical, biochemical, serological, and microbiome data for clinically meaningful subgroups of patients should permit the development of tools for individualized risk stratification and treatment selection.
遗传变异在炎症性肠病易感性中的作用的不断增加，预示着疾病分类的时代已经超越了克罗恩病和溃疡性结肠炎。更加强有力的炎症性肠病亚型的分子定义可能基于特定的分子途径，这些途径不仅决定疾病的易感性，而且决定疾病的特征，如位置、自然史和治疗反应。用于炎症性肠病的不断发展的诊断面板将包括临床变量和遗传标记，以及其他基因功能和与环境因素（如微生物组）相互作用的指标。将临床、血清学和遗传信息相结合的多模式算法可能有助于预测疾病进程。炎症性肠病易感性和药物相关途径基因的变异似乎影响了对 TNF 治疗的反应。此外，基因表达特征和综合模型都显示出作为治疗反应预测因子的潜力。最终，基于基因型和基因表达数据与临床、生化、血清学和微生物组数据相结合的模型，对于具有临床意义的患者亚组，应该可以开发出用于个体化风险分层和治疗选择的工具。
