Pharmacogenetics of Crohn's disease.
The considerable interindividual differences in efficacy and side effects of commonly used medications in Crohn's disease are partly owing to genetic polymorphisms. Many genetic variants have been studied in genes possibly involved in the metabolism or mechanism of action of therapeutic agents such as glucocorticosteroids, azathioprine/6-mercaptopurine, methotrexate, calcineurin inhibitors or anti-TNF agents. However, the only test translated into clinical practice is thiopurine S-methyltransferase (TPMT) genotyping for hematological toxicity of thiopurine treatment. To date, there are no other meaningful applications for pharmacogenomics in clinical practice of Crohn's disease. In the future, designed therapeutic trials should possibly permit the development of predictive models including genotypic markers, such as that proposed for the clinical outcome after infliximab therapy, which includes an apoptotic pharmacogenetic index. The recent identification of new susceptibility genes provides additional candidate markers that have possible effects on the outcomes of therapies, and prioritizes new therapeutic targets, such as the IL-23 pathway. Further innovative approaches might be relevant for the pharmacogenetic investigation of gene variants implied in innate immune pattern recognition and autophagy.
Török
Helga-Paula
HP
University of Munich, Department of Internal Medicine II, Campus Grosshadern, Marchioninistr. 15, D-81377 Munich, Germany. helga.toeroek@med.uni-muenchen.de
Göke
Burkhard
B
Konrad
Astrid
A
D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D000963:Antimetabolites / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D001682:Biological Availability; D003424:Crohn Disease / Q000188:drug therapy / Q000235:genetics / Q000276:immunology; D005938:Glucocorticoids / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D019384:Nucleic Acid Synthesis Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D010597:Pharmacogenetics
D000911:Antibodies, Monoclonal; D000963:Antimetabolites; D005938:Glucocorticoids; D019384:Nucleic Acid Synthesis Inhibitors