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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  • Additional Information
    • Source:
      Publisher: Reidel Country of Publication: Netherlands NLM ID: 0403234 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1573-4978 (Electronic) Linking ISSN: 03014851 NLM ISO Abbreviation: Mol Biol Rep Subsets: MEDLINE
    • Publication Information:
      Original Publication: Dordrecht, Boston, Reidel.
    • Subject Terms:
      Polymorphism, Single Nucleotide*; Heptanoic Acids/*therapeutic use ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/*therapeutic use ; Hypercholesterolemia/*drug therapy ; Organic Anion Transporters/*genetics ; Pyrroles/*therapeutic use ; Simvastatin/*therapeutic use; Adult ; Aged ; Alleles ; Atorvastatin ; Cholesterol, LDL/blood ; Drug Administration Schedule ; Female ; Gene Frequency ; Gene-Environment Interaction ; Haplotypes ; Humans ; Hypercholesterolemia/blood ; Hypercholesterolemia/genetics ; Hypercholesterolemia/physiopathology ; Liver-Specific Organic Anion Transporter 1 ; Male ; Middle Aged ; Organic Anion Transporters/blood ; Polymorphism, Restriction Fragment Length
    • 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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    • Accession Number:
      0 (Cholesterol, LDL)
      0 (Heptanoic Acids)
      0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors)
      0 (Liver-Specific Organic Anion Transporter 1)
      0 (Organic Anion Transporters)
      0 (Pyrroles)
      0 (SLCO1B1 protein, human)
      A0JWA85V8F (Atorvastatin)
      AGG2FN16EV (Simvastatin)
    • Publication Date:
      Date Created: 20140327 Date Completed: 20150202 Latest Revision: 20211021
    • Publication Date:
      20231215
    • Accession Number:
      10.1007/s11033-014-3334-z
    • Accession Number:
      24668570