1 Introduction. Thongprayoon C, Hansrivijit P, Kovvuru K, Kanduri SR, Bathini T, Pivovarova A, Smith JR, Cheungpasitporn W. J Clin Med. Genetic variants in the UDP-glucuronosyltransferase 1A1 gene predict the risk of severe neutropenia of irinotecan. A major progress in pharmacogenetics/pharmacogenomics has been possible thanks to the genetic revolution with the human genome project and the development of modern technologies in genetic testing. Molecular diagnosis of thiopurine S-methyltransferase deficiency: genetic basis for azathioprine and mercaptopurine intolerance. Article  (2020), Scientific Reports Schutz E, Gummert J, Mohr F, Oellerich M . Andersson T, Holmberg J, Rohss K, Walan A . Drug target genes may work in concert with genes that affect pharmacokinetic properties to contribute to overall drug response. Google Scholar. Raida M, Schwabe W, Hausler P, Van Kuilenburg AB, Van Gennip AH, Behnke D et al. Evans WE, Hon YY, Bomgaars L, Coutre S, Holdsworth M, Janco R et al. Lancet 1993; 341: 436. In many clinical trials which have been published recently, it could be shown that VKORC1 genetic polymorphisms also explain a large part of the variability in dose requirements of vitamin K antagonists and therefore, in addition to CYP2C9 polymorphism and demographic factors, play a dominant role in the determination of individual dose.69, 70, 71 Moreover, Sconce et al.69 proposed a dosing algorithm for individual adjustment of warfarin dose taking into account the CYP2C9 and VKORC1 genotype, age and height, however, such approach should be proved in prospective clinical studies before wide clinical implementation is possible. Clin Pharmacol Ther 2003; 74: 505–508. Thanks to modern pharmacogenomic technologies, it was found that genetic regulation of DMEs, like other proteins controlling biological processes in living organisms, is actually more complex than initially expected. Wedlund PJ . Zhou HH, Wood AJJ . Yasar U, Forslund-Bergengren C, Tybring G, Dorado P, Llerena A, Sjoqvist F et al. Impact of polymorphisms of cytochrome-P450 isoenzymes 2C9, 2C19 and 2D6 on plasma concentrations and clinical effects of antidepressants in a naturalistic clinical setting. Use of genetic backgrounds to help to guide warfarin dosing has been advocated for several years by the US Food and Drug Administration. Barrera-Pulido L, Aguilera-García I, Docobo-Pérez F, Alamo-Martínez JM, Pareja-Ciuró F, Nuñez-Roldán A, Gómez-Bravo MA, Bernardos-Rodríguez A. Genotypic analysis of thiopurine S-methyltransferase in patients with Crohn's disease and severe myelosuppression during azathioprine therapy. Prevalence of a common point mutation in the dihydropyrimidine dehydrogenase (DPD) gene within the 5′-splice donor site of intron 14 in patients with severe 5-fluorouracil (5-FU)-related toxicity compared with controls. Prasad N, Jaiswal A, Behera MR, Agarwal V, Kushwaha R, Bhadauria D, Kaul A, Gupta A. Kidney Int Rep. 2019 Sep 27;5(1):28-38. doi: 10.1016/j.ekir.2019.09.013. Pharmacogenetics of drug metabolising enzymes: importance for personalised medicine. It has been expected that personalized medicine considering patients’ individual genetic profile would soon be introduced into clinical practice. Kalow W . Clin Pharmacol Ther 1980; 28: 356–367. Am J Hum Genet 1997; 60: 284–295. On the pharmacokinetics side, mostly drug metabolism and elimination is affected, and this can be translated into clinical practice by giving, for example, dose adjustments. It is metabolized to acetylisoniazid by the hepatic enzyme N-acetyltransferase type 2 (NAT2). Furuta T, Shirai N, Takashima M, Xiao F, Hanai H, Sugimura H et al. Google Scholar. Expert Rev Mol Diagn. NCI CPTC Antibody Characterization Program. These genetic polymorphisms have large effects, extensively documented in studies of individual differences in drug clearance affecting therapy outcome and safety [8]. Pharmacogenomics J 8, 4–15 (2008). J Clin Oncol 2004; 22: 1382–1388. Whereas pharmacogenetics is focused on pharmacological consequences of a single gene mutation, pharmacogenomics tries to simultaneously consider numerous genes and their mutual interaction. DRUG TARGETS Genetic polymorphisms occur commonly for drug target proteins, including receptors, enzymes, ion channels, and intracellular signaling proteins. CYP2B6. Genetic Polymorphisms in Low-Dose Methotrexate Transporters ... is a transmembrane protein with 12 regions that plays an important role in drug absorption and distribution. Coumarin anticoagulants, which are vitamin K antagonists, belong to the most frequently prescribed drugs in the world and are characterized by a narrow therapeutic index with both interindividually and intraindividually varying effectiveness. Molecular diagnosis of TPMT deficiency in patients with severe 5-fluorouracil-associated toxicity: of!, Rietschel M, Wong ML, gram LF, Guentert TW M... 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