Update on the clinical pharmacogenomics of organ transplantation.
Organ transplantation suffers from a static graft and patient survival rate, and a high incidence of serious adverse drug effects. The pharmacogenomics of organ transplantation has emerged only recently and is complementary to the immunogenetic information that has accumulated over the past decade. Gene polymorphism studies have focused on the genes that interact across the group of immunosuppressants, including ciclosporin, tacrolimus, sirolimus and corticosteroids. The polymorphisms that hold the most potential for use in a drug selection algorithm are in genes CYP3A5, ABCB1, IMPDH1 and IMPDH2, and cytokines and growth factors. Gene-expression arrays have led to gene-expression testing, such as the use of AlloMap((R)) with heart transplant patients. The expanded use of gene-expression assays, proteomics and drug selection algorithms in organ transplantation will progress slowly and may be outpaced by drug test co-development programs for new transplant drugs. In the future, clinical pharmacogenomics will be a routine part of patient care for organ transplant patients.
Burckart
Gilbert J
GJ
Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, 10903 New Hampshire Avenue, Building 51, Room 3184, Silver Spring, MD 20993, USA. gilbert.burckart@fda.hhs.gov
Amur
Shashi
S
D000818:Animals; D015415:Biomarkers; D051544:Cytochrome P-450 CYP3A / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D055106:Genome-Wide Association Study; D014453:Glucuronosyltransferase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007168:IMP Dehydrogenase / Q000235:genetics / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics / Q000494:pharmacology; D016377:Organ Transplantation / Q000502:physiology* / Q000639:trends*; D010597:Pharmacogenetics / Q000639:trends*; D011110:Polymorphism, Genetic / Q000235:genetics
D015415:Biomarkers; D007166:Immunosuppressive Agents; D007168:IMP Dehydrogenase; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; C110655:UDP-glucuronosyltransferase, UGT1A6; D014453:Glucuronosyltransferase