title: Pharmacogenetics in inflammatory bowel disease.
abstract: Pharmacogenetics is the study of the association between variability in drug response and (or) drug toxicity and polymorphisms in genes. The goal of this field of science is to adapt drugs to a patient's specific genetic background and therefore make them more efficacious and safe. In this article we describe the variants in genes that influence either the efficacy or toxicity of common drugs used in the treatment of inflammatory bowel diseases (IBD), ulcerative colitis (UC), and Crohn's disease (CD) including sulfasalazine and mesalazine, azathioprine (AZA) and 6-mercaptopurine (6-MP), methotrexate (MTX), glucocorticosteroids (CSs) and infliximab. Furthermore, difficulties with pharmacogenetic studies in general and more specifically in IBD are described. Although pharmacogenetics is a promising field that already contributed to a better understanding of some of the underlying mechanisms of action of drugs used in IBD, the only discovery translated until now into daily practice is the relation between thiopurine S-methyltransferase (TPMT) gene polymorphisms and hematological toxicity of thiopurine treatment. In the future it is necessary to organize studies in well characterized patient cohorts who have been uniformly treated and systematically evaluated in order to quantitate drug response more objectively. An effort should be made to collect genomic DNA from all patients enrolled in clinical drug trials after appropriate informed consent for pharmacogenetic studies.
authors.affiliation: Department of Gastro-enterology, University of Hospital Gasthuisberg, Leuven, Belgium. marieke.pierik@uz.kuleuven.ac.be
authors.forename: Marie
authors.initials: M
authors.lastname: Pierik
authors.forename: Paul
authors.initials: P
authors.lastname: Rutgeerts
authors.forename: Robert
authors.initials: R
authors.lastname: Vlietinck
authors.forename: Severine
authors.initials: S
authors.lastname: Vermeire
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use; D001379:Azathioprine / Q000009:adverse effects / Q000627:therapeutic use; D003093:Colitis, Ulcerative / Q000188:drug therapy* / Q000235:genetics*; D003424:Crohn Disease / Q000188:drug therapy* / Q000235:genetics*; D005765:Gastrointestinal Agents / Q000009:adverse effects / Q000627:therapeutic use; D005938:Glucocorticoids / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use; D000069285:Infliximab; D015122:Mercaptopurine / Q000009:adverse effects / Q000627:therapeutic use; D019804:Mesalamine / Q000009:adverse effects / Q000627:therapeutic use; D008727:Methotrexate / Q000009:adverse effects / Q000627:therapeutic use; D008780:Methyltransferases / Q000235:genetics / Q000502:physiology; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D012460:Sulfasalazine / Q000009:adverse effects / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000911:Antibodies, Monoclonal; D005765:Gastrointestinal Agents; D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D012460:Sulfasalazine; D019804:Mesalamine; D000069285:Infliximab; D015122:Mercaptopurine; D008780:Methyltransferases; C022745:thiopurine methyltransferase; D001379:Azathioprine; D008727:Methotrexate