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Background: Polymorphisms in genes encoding drug transporters could be valuable pharmacogenetic markers. The ABCG2 efflux transporter is expressed in multiple tissues and plays an important role in the disposition of different drugs including statins. The functional 421C>A polymorphism in the ABCG2 that reduces transporter activity has been found to be associated with increased systemic exposures to certain statins, including fluvastatin. Although genetic variability in the ABCG2 distinctively affects the pharmacokinetics, there are no published data that would indicate that variability can result in fluvastatin induced adverse drug reactions (ADRs). The aim of this case-control study is to show the contribution of pharmacogenetic predisposition (ABCG2 gene variant) to the development of fluvastatin ADRs (myotoxicity, hepatotoxicity, other side effects) in renal transplant recipients. Patients and methods: 108 renal transplant recipients were included in the study, 54 patients with ADRs to fluvastatin therapy, and 54 controls without ADRs (matched according to fluvastatin dose, age, gender, concomitant therapy, and other conditions). Genotyping of the ABCG2 421C>A polymorphism was performed using the TaqMan allele-specific PCR assay (AppliedBiosystems). Results: According to the statistical analysis, ABCG2 421CA genotype carriers have significantly higher incidence of ADRs to fluvastatin therapy comparing to ABCG2 421CC genotype carriers (OR 3.77, 95%CI 1.26-11.28, P = 0.024). Conclusion: Our data are the first to indicate there is an association between adverse drug reactions to fluvastatin therapy in renal transplant recipients with ABCG2 421C>A polymorphism. |
