Pharmacogenetics in IBS: update and impact of GWAS studies in drug targets and metabolism

ABSTRACT

Introduction

Medications are frequently prescribed for patients with irritable bowel syndrome (IBS) or disorders of gut brain interaction. The level of drug metabolism and modifications in drug targets determine medication efficacy to modify motor or sensory function as well as patient response outcomes.

Areas covered

The literature search included PubMed searches with the terms: pharmacokinetics, pharmacogenomics, epigenetics, clinical trials, irritable bowel syndrome, disorders of gut brain interaction, and genome-wide association studies. The main topics covered in relation to irritable bowel syndrome were precision medicine, pharmacogenomics related to drug metabolism, pharmacogenomics related to mechanistic targets, and epigenetics.

Expert opinion

Pharmacogenomics impacting drug metabolism [CYP 2D6 (cytochrome P450 2D6) or 2C19 (cytochrome P450 2C19)] is the most practical approach to precision medicine in the treatment of IBS. Although there are proof of concept studies that have documented the importance of genetic modification of transmitters or receptors in altering responses to medications in IBS, these principles have rarely been applied in patient response outcomes. Genome-wide association (GWAS) studies have now documented the association of symptoms with genetic variation but not the evaluation of treatment responses. Considerably more research, particularly focused on patient response outcomes and epigenetics, is essential to impact this field in clinical medicine.

KEYWORDS:

• Treatment
• cytochrome P450
• serotonergic
• epigenetics
• irritable bowel syndrome

Article highlights

• Pharmacogenomics impacting drug metabolism (CYP 2D6 or 2C19) is the most practical approach to precision medicine in the treatment of IBS.

• Proof-of-concept studies have documented the importance of genetic modification of transmitters or receptors in altering responses to medications in IBS, e.g. serotonergic transporter and colonic transit.

• GWAS studies have documented the association of symptoms with genetic variations.

• The principles of pharmacogenomics related to drug targets, GWAS and epigenetics have rarely been applied in patient response outcomes in IBS.

• Future research focused on patient response outcomes and epigenetics is essential to impact the application of precision genetic medicine to the field of IBS.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Acknowledgments

The authors thank C Stanislav for secretarial assistance.

Additional information

Funding

This manuscript was in part funded by NIH [5T32-DK719848].