PharmGKB very important pharmacogene: SLCO1B1

Abstract

The solute carrier organic anion transporter family member 1B1 (SLCO1B1) gene encodes for a membrane-bound sodium-independent organic anion transporter protein (OATP1B1) that is involved in active cellular influx of many endogenous and xenobiotic compounds. SLCO1B1, formerly known by several other names including organic anion transporter 2 (OATP2), OATPC, liver-specific transporter 1 (LST1), and SLC21A6, is located on chromosome 12 and encodes a 691 amino acid protein with 12 transmembrane helices [1,2]. The gene is a member of the family of SLC21 (human: OATP, rodent: Oatp) transporters [3,4]. OATP1B1 is expressed predominantly on the basolateral membrane of hepatocytes [5,6], where it mediates active intracellular hepatic transport of various anionic compounds [5,6]. The protein sequence of OATB1B1 is similar to those of other organic anion transporters. The human protein shares 64% sequence identity with rOatp4 and 65% sequence identity with mOatp4 and 44–47% with other rodent Oatps [3]. Compared with other members of the human organic anion transporters, OATP1B1 is the most similar to OATP1B3 (SLCO1B3, previously known as SLC21A8). These two proteins share 80% amino acid sequence identity, are expressed predominantly in the liver, and have similar substrate selectivity [1]. Functionality between these two human transporters in the SLC21 family can be distinguished using estrone-3-sulfate, an OATP1B1-selective ligand, and cholecystokinin octapeptide, an OATP1B3-selective ligand [7]. Note that the selectivity for estrone sulfate applies only in distinguishing the transport between OATP1B1 versus OATP1B3; estrone sulfate is an excellent substrate for other organic anion transporters, such as OAT3 (SLC22A9)[8]. Recent reviews describe the role of OATP1B1 in general drug disposition [2] and, specifically, in 3-hydroxy-3-methyl-glutaryl-CoEnzyme A reductase reductase inhibitor (statin) pharmacokinetics [9]. As OATP1B1 mediates intrahepatic transport of pharmaceutical agents, SLCO1B1 is an important pharmacokinetic gene – and, as described below, an important pharmacogene.