title: Polymorphism of the hepatic influx transporter organic anion transporting polypeptide 1B1 is associated with increased cholesterol synthesis rate.
abstract: We investigated the influence of SLCO1B1 polymorphism on cholesterol synthesis and absorption during baseline, and as affected by statins. In a crossover study, 32 healthy volunteers with different SLCO1B1 genotypes ingested a single dose of fluvastatin, pravastatin, simvastatin, rosuvastatin, and atorvastatin. Plasma total cholesterol, and cholesterol synthesis and absorption markers were measured before statin administration and up to 12 h thereafter. The mean fasting baseline plasma desmosterol to cholesterol ratio was 40% higher in participants with the SLCO1B1 c.521CC variant genotype than in those with the c.521TT genotype (P=0.043). The genotype had no significant effect on cholesterol absorption markers. All statins decreased lathosterol and avenasterol to cholesterol ratios, but no significant differences in the response existed between SLCO1B1 genotypes. In conclusion, the low activity SLCO1B1 c.521CC genotype is associated with an increased cholesterol synthesis rate. The short-term effects of statins on cholesterol homeostasis were not associated with the SLCO1B1 polymorphism.
authors.affiliation: Department of Clinical Pharmacology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Marja K
authors.initials: MK
authors.lastname: Pasanen
authors.forename: Tatu A
authors.initials: TA
authors.lastname: Miettinen
authors.forename: Helena
authors.initials: H
authors.lastname: Gylling
authors.forename: Pertti J
authors.initials: PJ
authors.lastname: Neuvonen
authors.forename: Mikko
authors.initials: M
authors.lastname: Niemi
mesh_terms: D002784:Cholesterol / Q000378:metabolism*; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D008099:Liver / Q000378:metabolism*; D027381:Liver-Specific Organic Anion Transporter 1; D026901:Membrane Transport Proteins / Q000378:metabolism; D008954:Models, Biological; D027361:Organic Anion Transporters / Q000235:genetics* / Q000378:metabolism; D010597:Pharmacogenetics / Q000379:methods; D011110:Polymorphism, Genetic; D013997:Time Factors
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D027381:Liver-Specific Organic Anion Transporter 1; D026901:Membrane Transport Proteins; D027361:Organic Anion Transporters; C503999:SLCO1B1 protein, human; C001521:lathosterol; D002784:Cholesterol