Pharmacogenetics and the treatment of functional gastrointestinal disorders

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.

Keywords: CYP450; bile acid; cannabinoid; pharmacodynamics; pharmacokinetics; serotonergic; serotonin transporter.