engleski

Pharmacogenomics of rosuvastatin – impact of ABCG2 and SLCO1B1 polymorphisms and drug-drug interactions on development of adverse drug reactions

Introduction: ABCG2 c.421C>A and SLCO1B1 c.521T>C polymorphisms are associated with a reduced transporter function and higher exposure to rosuvastatin. We investigated the relationship between ABCG2 and SLCO1B1 polymorphisms, drugdrug interactions (DDIs) and rosuvastatin-related myotoxicity and hepatotoxicity. Patients and methods: In this case-control study, cases were subjects that developed rosuvastatinrelated myotoxicity and hepatotoxicity and control subjects were rosuvastatin-treated patients free of adverse drug reactions (ADRs). Patients were enrolled retrospectively and prospectively for 3, 5 years, and their clinical data, concomitant therapy and rosuvastatin-related myotoxicity and hepatotoxicity occurrence were evaluated. All subjects were genotyped for ABCG2 c.421C>A and SLCO1B1 c.521T>C by TaqMan® real-time PCR method. Using the individuals' medication lists and Lexicomp® clinical decision support system, the prevalence of DDI and drug-drug- gene interactions (DDGIs) were analysed. Results: A total of 356 subjects were recruited (cases (n=128), controls (n=228)). SLCO1B1 c.521T>C variant carriers had 1, 4- times greater odds (95% CI: 0, 92-2, 20 ; χ² = 6, 333 ; p=0, 042), and ABCG2 c.421C>A variant carriers had 1, 9-times greater odds (95% CI: 1, 18- 3, 33 ; χ² = 6, 814 ; p=0, 009) of developing rosuvastatin ADRs. The number of clinically relevant DDI that could have contributed to ADRs was low, both in a group of cases (n=16) and in a control group (n=50). There was no statistically significant difference in the rate of DDGIs between both groups. Conclusions: In our study, preliminary data showed an association between ABCG2 c.421C>A and SLCO1B1 c.521T>C polymorphisms and rosuvastatin- related myotoxicity and hepatotoxicity. At the same time, there was no association between rosuvastatin DDIs, ABCG2 and SLCO1B1 polymorphisms and rosuvastatin- related ADR

ABCG2 ; SLBO1B1 ; polymorphisms ; rosuvastatin

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