title: No impact of SLCO1B1 521T>C, 388A>G and 411G>A polymorphisms on response to statin therapy in the Greek population.
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.
authors.affiliation: Laboratory of Pharmacology, Medical School, Democritus University of Thrace, Dragana Campus, 68100, Alexandroupolis, Greece.
authors.forename: E
authors.initials: E
authors.lastname: Giannakopoulou
authors.forename: G
authors.initials: G
authors.lastname: Ragia
authors.forename: V
authors.initials: V
authors.lastname: Kolovou
authors.forename: A
authors.initials: A
authors.lastname: Tavridou
authors.forename: A D
authors.initials: AD
authors.lastname: Tselepis
authors.forename: M
authors.initials: M
authors.lastname: Elisaf
authors.forename: G
authors.initials: G
authors.lastname: Kolovou
authors.forename: V G
authors.initials: VG
authors.lastname: Manolopoulos
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D000069059:Atorvastatin; D008078:Cholesterol, LDL / Q000097:blood; D004334:Drug Administration Schedule; D005260:Female; D005787:Gene Frequency; D059647:Gene-Environment Interaction; D006239:Haplotypes; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D027381:Liver-Specific Organic Anion Transporter 1; D008297:Male; D008875:Middle Aged; D027361:Organic Anion Transporters / Q000097:blood / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D011758:Pyrroles / Q000627:therapeutic use*; D019821:Simvastatin / Q000627:therapeutic use*
chemical_list: D008078:Cholesterol, LDL; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D027381:Liver-Specific Organic Anion Transporter 1; D027361:Organic Anion Transporters; D011758:Pyrroles; C503999:SLCO1B1 protein, human; D000069059:Atorvastatin; D019821:Simvastatin