No impact of SLCO1B1 521T>C, 388A>G and 411G>A polymorphisms on response to statin therapy in the Greek population |
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Authors: | E Giannakopoulou G Ragia V Kolovou A Tavridou A D Tselepis M Elisaf G Kolovou V G Manolopoulos |
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Institution: | 1. Laboratory of Pharmacology, Medical School, Democritus University of Thrace, Dragana Campus, 68100, Alexandroupolis, Greece 2. Cardiology Department, Onassis Cardiac Surgery Center, Athens, Greece 3. Clinical Pharmacology Unit, Academic General Hospital of Alexandroupolis, Alexandroupolis, Greece 4. Department of Chemistry, University of Ioannina, Ioannina, Greece 5. Department of Internal Medicine, School of Medicine, University of Ioannina, Ioannina, Greece
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Abstract: | Interindividual variability exists in statin lipid-lowering response, partially attributed to genetic factors. Organic anion-transporting polypeptide 1B1 (OATP1B1) encoded by SLCO1B1 gene (solute carrier organic anion transporter family member 1B1) facilitates hepatic uptake of simvastatin and atorvastatin. SLCO1B1 polymorphisms are strongly associated with statin-induced myopathy whereas few studies have assessed their effect on statin differential response. In the present study, we analyzed the association of SLCO1B1 521T>C, 388A>G and 411G>A polymorphisms with response to atorvastatin and simvastatin in 386 adults (201 atorvastatin-treated and 185 simvastatin-treated) with primary hypercholesterolemia, all of Greek origin. Total cholesterol and low-density lipoprotein cholesterol were measured at baseline and on 6 months of treatment. Genetic polymorphisms were analyzed by polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) method. A novel RFLP protocol was developed for the simultaneous identification of 388A>G and 411G>A polymorphisms. SLCO1B1 521T>C, 388A>G and 411G>A polymorphisms were not associated with lipid-lowering response to atorvastatin or simvastatin. No sex-gene or statin dose-gene interaction was observed on the effect of the analyzed SLCO1B1 polymorphisms in statin lipid lowering response in either statin-treated patient cohort. Further studies in different populations are required to draw firm conclusion on the potential association of SLCO1B1 polymorphisms with statin lipid-lowering response. |
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