Pharmacogenetics in clinical practice – Recommendations and guidelines

Variability in the eff ect of a drug can be partially explained by genetic diff erences. There are interindividual diff erences in metabolic and transport capacity and detoxifi cation of drugs and other xenobiotics. Sensitivity to toxic eff ects partly depends on the genetic polymorphism of metabolic enzymes of phase I and phase II. For clinical practice, the most important polymorphisms in phase I are CYP2C9, CYP2C19, CYP2D6 and CYP3A4/5, and in phase II TPMT, UGT1A1, NAT2, SULT. The clearest impact have inactivating alleles and alleles with increased CYP2C19 eff ect on the outcome of treatment with clopidogrel, as well as serious side eff ects to the use of codeine in ultrarapid metabolizers of CYP2D6. Another signifi cant impact is observed in case of ineff ectiveness of antidepressants, suicidality in ultrarapid metabolizers, and medication side eff ects in poor metabolizers of CYP2D6. Carriers of inactive CYP2C9 alleles are at an increased risk of overdose with drug substrates, which can lead to intoxication with phenytoin, or bleeding in case of coumarin anticoagulants or NSAIDs. There are guidelines for TPMT genotyping in case of thiopurine drug treatment, as well as recommendations for the analysis of UGT1A1 for irinotecan therapy optimization and DPYD genotyping in case of the use of 5-fl uorouracil. One of transport proteins recommended for genotyping is SLCO1B1 for better prevention of side eff ects in the use of statins. Latest guidelines emphasize strong predisposition in the carriers of HLA-B * 5701 allele for the development of hypersensitivity to abacavir. For better understanding of variable eff ectiveness of drugs in pediatric population, it is necessary, along with genetic predisposition, to understand the diff erences in gene expression during growth and development, i.e. ontogenesis.

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