The focus of this program is on molecular markers in body fluids that predict the effectiveness and toxicities of therapeutic interventions. In particular, the contribution of genetic predisposition of enzymes involved in the metabolism of endogenous and exogenous substrates is investigated. Part of this research programm is focussed on endogenous methylation and methyl-group metabolism in relation to vascular disease and oncology (project leaders Prof. Dr. Jan Lindemans and Dr. Robert de Jonge). The translational research performed is aimed to identify and evaluate the clinical significance of genetic polymorphisms (SNPs/haplotypes) in relation to pharmacokinetic and pharmacodynamics of medicines. Targets are genes encoding drug metabolizing enzymes (a.o. cytochrome P450s, UGTs) and drug transporters (a.o. MDR1, MRP2, etc). Ultimate aim is to develop and incorporate clinically significant pharmacogenetic tests for routine patient care. Specific research topics include pharmacogenetics of folate antimetabolites (methotrexate, pemetrexed, collaboration with Depts. Rheumatology, Neurology and Pulmonology), immunosuppressives (collaboration with Dept. Hospital Pharmacy), drugs in oncology (tamoxifen and taxanes, collaboration with Dept. Medical Oncology), anti-depressants and anti-epileptics (collaboration with Dept. Psychiatry), anaesthetics (collaboration with Dept. Anesthesiology), anti-virals (collaboration with Dept. Internal Medicine), anti-coagulation drugs (collaboration with Dept. Epidemiology & Biostatistics) and opioids (collaboration with Depts. Children s Surgery and Medical Oncology).