No impact of SLCO1B1 521T>C, 388A>G and 411G>A polymorphisms on response to statin therapy in the Greek population

• Published in: Molecular biology reports Vol. 41; no. 7; pp. 4631 - 4638
• Main Authors: Giannakopoulou, E, Ragia, G, Kolovou, V, Tavridou, A, Tselepis, A. D, Elisaf, M, Kolovou, G, Manolopoulos, V. G
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer-Verlag 01.07.2014; Springer Netherlands; Springer Nature B.V
• Subjects: Adult; adults; Aged; Alleles; Animal Anatomy; Animal Biochemistry; Atorvastatin Calcium; Biomedical and Life Sciences; cholesterol; Cholesterol, LDL - blood; Drug Administration Schedule; Female; Gene Frequency; Gene-Environment Interaction; genes; genetic polymorphism; Genomics; Haplotypes; Heptanoic Acids - therapeutic use; Histology; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use; hypercholesterolemia; Hypercholesterolemia - blood; Hypercholesterolemia - drug therapy; Hypercholesterolemia - genetics; Hypercholesterolemia - physiopathology; Life Sciences; low density lipoprotein; Male; Middle Aged; Morphology; muscular diseases; Organic Anion Transporters - blood; Organic Anion Transporters - genetics; patients; Pharmacology; Polymorphism; Polymorphism, Restriction Fragment Length; Polymorphism, Single Nucleotide; polypeptides; Pyrroles - therapeutic use; Simvastatin - therapeutic use; Solute Carrier Organic Anion Transporter Family Member 1b1; solutes; Statins; therapeutics; Response; Atorvastatin; Hypercholesterolemia; Simvastatin; Pharmacogenomics
• ISSN: 0301-4851; 1573-4978
• DOI: 10.1007/s11033-014-3334-z

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.