Electronic Thesis and Dissertation Repository

Degree

Master of Science

Program

Pharmacology and Toxicology

Supervisor

Richard Kim

Abstract

Statin-induced myopathy is a common adverse reaction of statin therapy. Patients with elevated plasma concentration of statins are thought to be at greater risk for myopathy. Statins are transported from the blood to hepatocytes via organic anion transporting polypeptide 1B1 (OATP1B1). Although single nucleotide polymorphisms (SNPs) in OATP1B1 have been associated with increased statin concentrations, we hypothesize that there may be other SNPs in OATP1B1 that can also contribute to reduced transport activity and increased plasma statin concentrations. OATP1B1 cDNA packaged in pEF6/V5-His TOPO was used as template, and 6 SNPs — c.298G>A, c.419C>T, c.463C>A (*4), c.1007C>G, c.1463G>C (*9), and c.1738C>T — were introduced separately and expressed in adenovirus. 3 SNPs abolished transport activity, 1 SNP decreased transport, 1 increased transport, and 1 did not affect transport activity. Our data support the hypothesis that there are additional loss of function SNPs in OATP1B1.


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Pharmacology Commons

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