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Function impairing polymorphisms of the hepatic uptake transporter SLCO1B1 modify therapeutic efficacy of statins in a population based cohort
JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift)
ID 2719931
Author(s) Meyer zu Schwabedissen, H. E.; Albers, M.; Baumeister, S. E.; Rimmbach, C.; Nauck, M.; Siegmund, W.; Voelzke, H.; Kromer, H. K.
Author(s) at UniBasel Meyer zu Schwabedissen, Henriette
Year 2015
Title Function impairing polymorphisms of the hepatic uptake transporter SLCO1B1 modify therapeutic efficacy of statins in a population based cohort
Journal Pharmacogenetics and genomics
Volume 25
Number 1
Pages / Article-Number 8-18
Keywords drug efficacy, hypercholesterolaemia, OATP1B1, statins
Mesh terms Adult; Aged; Aged, 80 and over; Biomarkers, Pharmacological; Coronary Disease, pathology; Fatty Acids, Monounsaturated, administration & dosage; Female; Genetic Association Studies; Genotype; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors, administration & dosage; Indoles, administration & dosage; Lipid Metabolism, genetics; Lovastatin, genetics; Male; Middle Aged; Organic Anion Transporters, genetics; Pravastatin, genetics; Risk Assessment; Simvastatin, administration & dosage; Solute Carrier Organic Anion Transporter Family Member 1b1
Abstract BackgroundThe efficacy of statins, which are used commonly in primary and secondary prevention of cardiovascular diseases, shows a wide range of interindividual variability. Genetic variants of OATP1B1, a hepatic uptake transporter, can modify access of statins to its therapeutic target, thereby potentially altering drug efficacy. We studied the impact of genetic variants of OATP1B1 on the lipid-lowering efficacy of statins in a population-based setting.Materials and methodsThe basis of the analysis was the Study of Health in Pomerania, a cohort of 2732 men and women aged 20-81 years. Included in the statistical analysis to evaluate the impact of OATP1B1 on therapeutic efficacy of statins were 214 individuals diagnosed with dyslipidaemia during initial recruitment and receiving statins during the 5-year follow-up.ResultsAnalysing the impact of the OATP1B1 genotype, we observed a trend for lower statin-induced total cholesterol reduction in carriers of the SLCO1B1 512C variant. Restricting the analysis to patients receiving simvastatin, pravastatin, lovastatin and fluvastatin indicated a statistically significant association of the OATP1B1 genotype on lipid parameters at the 5-year follow-up. No such effect was observed for atorvastatin. Calculation of achievement of treatment goals according to the NCEP-ATPIII guidelines showed a lower rate of successful treatment when harbouring the mutant allele for patients taking simvastatin (46.7 vs. 73.9%). A similar trend was observed for pravastatin (34.4 vs. 70.4%).ConclusionGenetic variants of OATP1B1 leading to impaired hepatic uptake of statins translated into reduced drug efficacy in a population-based cohort. (C) 2014 Wolters Kluwer Health vertical bar Williams & Wilkins.
Publisher Lippincott Williams & Wilkins
ISSN/ISBN 1744-6872
Full Text on edoc Available
Digital Object Identifier DOI 10.1097/FPC.0000000000000098
PubMed ID
ISI-Number WOS:000346632900002
Document type (ISI) Article

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