药物遗传学与功能性胃肠疾病的治疗

Pharmacogenetics and the treatment of functional gastrointestinal disorders.

作者信息

Halawi Houssam, Camilleri Michael

机构信息

Clinical Enteric Neuroscience Translational & Epidemiological Research (C.E.N.T.E.R.), Division of Gastroenterology & Hepatology, Mayo Clinic, Rochester, MN 55905, USA.

出版信息

Pharmacogenomics. 2017 Jul;18(11):1085-1094. doi: 10.2217/pgs-2017-0049. Epub 2017 Jul 7.

Abstract

The diagnosis and management of functional gastrointestinal disorders (FGIDs) remain very challenging. In the era of precision medicine, it is important to individualize the treatment of these conditions by providing targeted and effective therapies while minimizing the risk of medication side effects. By using genetic information that predicts and affects the responses to specific medications, it is anticipated that the science of pharmacogenetics in FGIDs will advance the practice of precision medicine. The pathophysiology of FGIDs is complex, involving the interaction between predisposing genetic and environmental factors. Studies have shown that genetic polymorphisms may contribute to the variable responses to specific medications among individuals with FGIDs. Genetic variations in the CYP450 system can affect the metabolism and, hence, the pharmacokinetics of drugs used to treat FGIDs. Polymorphisms in the genes controlling proteins that are involved in the direct action of medications targeting the serotonergic, cannabinoid, adrenergic and bile acid pathways can affect the pharmacologic effects of the medications. In this review, we summarize the published literature on the pharmacogenetics of FGIDs and address the potential clinical utility and future challenges in this field. Since it was the dominant topic in the majority of the articles relevant to FGIDs, our review will focus on irritable bowel syndrome.

摘要

功能性胃肠疾病(FGIDs)的诊断和管理仍然极具挑战性。在精准医学时代,通过提供针对性强且有效的治疗方法,同时将药物副作用风险降至最低,对这些病症进行个体化治疗非常重要。通过利用能够预测并影响对特定药物反应的基因信息,预计FGIDs领域的药物遗传学将推动精准医学实践的发展。FGIDs的病理生理学很复杂,涉及遗传易感性因素与环境因素之间的相互作用。研究表明,基因多态性可能导致FGIDs患者个体对特定药物的反应存在差异。细胞色素P450(CYP450)系统中的基因变异会影响药物代谢,进而影响用于治疗FGIDs的药物的药代动力学。控制参与靶向5-羟色胺能、大麻素、肾上腺素能和胆汁酸途径的药物直接作用的蛋白质的基因多态性,会影响药物的药理作用。在本综述中,我们总结了已发表的关于FGIDs药物遗传学的文献,并探讨了该领域潜在的临床应用价值和未来挑战。由于它是大多数与FGIDs相关文章中的主要主题,我们的综述将聚焦于肠易激综合征。

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