The role of pharmacogenetics in nonmalignant gastrointestinal diseases

Abstract

Genetic variation influences the absorption and efflux of drugs in the intestine, the metabolism of drugs in the liver and the effects of these drugs on their target proteins. Indeed, variations in genes whose products have a role in the pathophysiology of nonmalignant gastrointestinal diseases, such as IBD, have been shown to affect the response of patients to therapy. This Review provides an overview of pharmacogenetics in the management of nonmalignant gastrointestinal diseases on the basis of data from clinical trials. Genetic variants that have the greatest effect on the management of patients with IBD involve the metabolism of thiopurines. Variation in drug metabolism by cytochrome P450 enzymes also requires attention so as to avoid drug interactions in patients receiving tricyclic antidepressants and PPIs. Few genotyping tests are currently used in the clinical management of patients with nonmalignant gastrointestinal diseases, owing to a lack of data from clinical trials showing their effectiveness in predicting nonresponse or adverse outcomes. However, pharmacogenetics could have a beneficial role in enabling pharmacotherapy for nonmalignant gastrointestinal diseases to be targeted to the individual patient.

Role of cytochrome P450 polymorphisms and functions in development of ulcerative colitis

“…To date, there are 3257 SNPs described for CYP2D6 in NCBI dbSNP (https://, access date: February 23, 2019). CYP2D6 is another isoform that genotyping and phenotyping are not usually performed for gastroenterological inflammation, on the assumption that the irrelativity of the medications to intestinal digestion or generally little metabolic limit of CYP2D6 in the small digestive tract[57,58]. CYP2D6 is another isoform on which genotyping and phenotyping are not usually performed for gastroenterological inflammation, on the belief that there is non-relativity of the medications to intestinal metabolism or the generally little metabolic limit of CYP2D6 in the small intestine[57,58].…”

“…In addition, CYP3A4/5 expressers require that particular attention should be paid to the onset of nephrotoxicity. Thus, genotyping for CYP3A5 variants allows individualised care to be practised[57,108,110,115,116].…”

Novel Diet, Drugs, and Gastric Interventions for Gastroparesis

“…42 Erythromycin is extensively metabolized by cytochrome P450 CYP3A. Many commonly used medications inhibit the effects of CYP3A (reviewed elsewhere 43 ) and may increase plasma erythromycin concentrations, increasing the risk of ventricular arrhythmias and sudden death. 44 …”

Personalized management in functional gastrointestinal disorders based on genomics: hope at last or just feigned praise?

“…One copy of the short variant allele ( 5-HTTLPR*LS ) is enough to cause decreased SERT transcription 24 and, subsequently, to cause increased serotonin activation of the postsynaptic neuron, which then leads to accelerated colonic transit. 25…”