Association between a frequent allele of the gene encoding OATP1B1 and enhanced LDL-lowering response to fluvastatin therapy

Introduction: Marked lowering of low-density-lipoprotein cholesterol (LDL-C) levels (≤50%) with intensive statin therapy is associated with major reduction in cardiovascular risk, but is limited by a potential increase in adverse effects, thereby justifying optimization of LDL-C reduction with minimal risk. The organic anion transporting polypeptide-1B1 encoded by the SLCO1B1 gene is implicated as a major transporter in cellular uptake of statins, and notably fluvastatin. We postulated that genetic variation in SLCO1B1 might affect statin bioavailability, and might therefore influence drug response and potential adverse effects. Materials & methods: Elderly hypercholesterolemic subjects (n = 724), whose plasma lipid profile was determined before and 2 months after fluvastatin extended-release treatment (80 mg/day, n = 420), or placebo (n = 304), were genotyped for the most frequent nonsynonymous polymorphisms (SNP) in the SLCO1B1 gene (c.388A>G, c.463C>A and c.521T>C). Results: Due to linkage disequilibri...