Editorial [Hot topic: Pharmacogenetics: Current Status and Future Perspectives (Executive Editor: Henk-Jan Guchelaar)]

Long before the term pharmacogenetics was coined, it was recognized that patients respond very differently to treatment with a drug. Indeed, the question how variability of drug response can be explained is as old as the science of pharmacology. The concept of interindividual differences in drug response was proposed as early as 1909 by Garrod in his book The Inborn Errors of Metabolism [1]. Only since the late 50s of the last century it was shown that variations in DNA may play a role in variable drug response. In 1957, Motulsky was the first to describe that some American soldiers of African descent were sensitive to the antimalarial drug primaquine [2]. It caused hemolytic anemia in a subgroup of primaquine users which could be ascribed to a deficiency of the enzyme glucose-6-phosphate dehydrogenase (abbreviated G6PD), a metabolic enzyme involved in the pentose phosphate pathway, and especially important in red blood cell metabolism. Moreover, it was recognized that some patients experienced muscle-relaxation for hours, sometimes necessitating artificial ventilation, instead of minutes after the administration of the muscle-relaxant suxamethonium. A deficiency of the enzyme pseudocholinesterase, involved in the degradation of the drug, causes this extraordinary drug response to suxamethonium [3]. In 2003 the International Human Genome Sequencing Consortium declared that the Human Genome Project had been completed, raising expectations of clinical application in the near future. Pharmacogenetics is one of the first clinical applications of the postgenomic era. It promises personalized medicine rather than the established “one size fits all” approach to drugs and dosages. The expected reduction in “trial and error drug treatment” should ultimately lead to more efficient and safer drug therapy [4]. Today, the concept of pharmacogenetics, namely that variation in drug response is related to genetic variation, is widely recognized. Commercially available pharmacogenetic tests have been approved by the Food and Drug Administration (FDA). These commercial tests detect variations in the genes coding for enzymes involved in drug metabolism, for example cytochrome P450 CYP2C19 and CYP2D6 or UDP-glucuronosyltransferase or in drug targets such as Vitamin K epoxide reductase complex, subunit 1 (abbreviated VKORC1) which is the drug target for the cumarins such as warfarin. However, it appears that the application of these and other pharmacogenetic tests in patient care remains limited. More generally, the implementation of pharmacogenetics in routine clinical practice presents significant challenges [4]. Providing scientific evidence for improved outcome in patient care by pharmacogenetic testing is one such challenge. In addition, for most pharmacogenetic tests (such as tests for genetic variants of cytochrome P450 enzymes) a detailed knowledge of pharmacology is a prerequisite for application in clinical practice, and clinicians might find it difficult to interpret the clinical value of pharmacogenetic test results. Guidelines that link the result of a pharmacogenetic test to therapeutic recommendations might help to overcome these problems, and have become available only recently [5,6]. Major developments in pharmacogenetics are seen in several clinical areas. In the present special issue the current status of pharmacogenetics and future perspectives in the field of psychiatry, inflammatory bowel disease, oncology, rheumatology, renal transplantation and anticoagulant therapy are described. In addition, the role of pharmacogenetics in phase I and II drug metabolism and in drug transporters is discussed. Finally, valuable papers on laboratory techniques, pharmacogenetics and drug design and development, and ethics of pharmacogenetic testing are included. A variety of internationally recognized experts have contributed to this special issue and compiled an excellent overview of the dynamic and promising field of pharmacogenetics.