Pharmacogenomics and Functional Gastrointestinal Disorders

Abstract

Functional gastrointestinal disorders, including irritable bowel syndrome and functional dyspepsia, are highly prevalent disorders affecting approximately one in four people in Western societies. This article reviews examples of the role of pharmacogenomics in the safety and efficacy of medications used in the management of such disorders. These include variations in the effects of medications metabolized by cytochrome P450 enzymes (e.g., 2D6 and 2C19), and the effects of genetic polymorphisms in the promoter of the serotonin transporter protein, which influence the response to alosetron in patients with diarrhea-predominant irritable bowel syndrome. These observations suggest that pharmacogenomics will introduce a new era in pharmacotherapeutics in gastroenterology.

Keywords::

• alosetron
• codeine
• CYP 450
• diarrhea
• dyspepsia
• gastroenterology
• GNβ3
• irritable bowel syndrome
• nortryptiline
• serotonergic antagonist
• SERT-P

Acknowledgment

Dr Camilleri is supported by grants R01-DK54681, R01-DK067071 and K24-DK02638 from the National Institutes of Health.

Figure 2. Colonic transit at 24 and 48 h in individual patients with IBS and either a (A) long polymorphism or (B) heterozygous polymorphism of the promoter region of SERT.

Figure 3. Association of SERT polymorphisms with colonic transit response to alosetron in patients with diarrhea-predominant irritable bowel syndrome.