Pharmacogenetics and diseases of the colon.
OBJECTIVE
The deciphering of the human genome sequence has enabled the identification of genetic polymorphisms that are responsible for inter-individual variation in the response to drug therapy. This field is referred to as pharmacogenetics. We review the impact of pharmacogenetics on therapy in diseases of the colon using three common variant enzyme systems as examples.


RESULTS
Many enzyme systems impact the treatment of diseases of the colon. Examples include thiopurine S-methyltransferase, dihydropyrimidine dehydrogenase and flavin monooxygenase 3. They affect the management of inflammatory bowel disease, colorectal cancer and the chemoprevention of colorectal adenoma by influencing the metabolism of their respective substrates, azathioprine/6-mercaptopurine, 5-fluorouracil and sulindac. Recent studies have implicated the significance of genetic polymorphisms in each of the three drug-metabolizing enzymes, which impacts on the therapeutic outcome of the stated diseases. These studies highlight the potential role of pharmacogenetics in the design of a therapeutic plan which would increase efficacy and limit toxicity.


CONCLUSIONS
Pharmacogenetics of drug-metabolizing systems continues to gain significance in the drug therapy of a variety of disease states including those of the gastrointestinal tract.
Hisamuddin
Irfan M
IM
Division of Digestive Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
Wehbi
Mohammad A
MA
Yang
Vincent W
VW
D003108:Colonic Diseases / Q000188:drug therapy* / Q000235:genetics*; D006801:Humans; D010597:Pharmacogenetics