Annotated PGx Gene Information for SLCO1B1
Submitted by: Lara Mangravite(PARC)
Reviewed by: Reviewed
Submitted date: June 23, 2006
| Gene HGNC Name: | SLCO1B1 |
|---|---|
| Gene Common Name: | SLCO1B1 |
| Introductory Information: |
SLCO1B1 is a sodium-independent organic anion transporter involved in cellular influx of naturally occurring and xenobiotic anionic compounds. Substrates include physiologically relevant compounds such as conjugated steroids, eicosanoids, and thyroid hormones as well as a number of clinically prescribed drugs including HMG-CoA reductase inhibitors or statins [PMID: 10397612]. Expressed predominantly on the basolateral membrane of hepatocytes, SLCO1B1- mediated influx is important for biliary excretion of bile acids as well as clinically administered compounds [PMID: 10601278, 10644574 ]. This may be particularly important for elimination of pravastatin over other statins, which are more hydrophobic and can more easily pass through cellular membranes by diffusion. The SLCO1B1 gene spans fifteen exons and is located on chromosome 12 between SLCO1B3 and SLCO1A2. The most common nonsynonymous variants of SLCO1B1, N130D and V174A, are represented alone or together as haplotypes *1A (neither), *1B (N130D), *5 (V174A) and *15 (N130D, V174A) [PMID: 12130747]. There is one additional haplotype, SLCO1B1*17, defined by the presence of a third promoter region variant, G-11187A, in addition to the two more commonly studied variants [PMID: 15864131]. There is conflicting evidence as to the in vitro functional or in vivo pharmacokinetic significance of these variants. Functional evidence suggests that presence of T521C (V174A) but not A388G (N130D) results in reduced maximal transport velocity (Vmax), possibly by intercellular sequestration and reduced surface exposure [PMID: 15970799, 15564882, 12130747]. In vivo pharmacokinetic studies, largely focused on pravastatin, associate presence of SLCO1B1*5, SLCO1B1*15, or SLCO1B1*17 with elevated pravastatin plasma AUC (area under the curve), implying reduced hepatocellular uptake and attenuated clearance [PMID:15226675, 15116054, 12811365, 15864131]. Presence of SLCO1B1*1B was associated with reduced pravastatin plasma AUC [PMID: 15226675]. SLCO1B1 variant-mediated alterations to pravastatin pharmacokinetics may affect cholesterol response to pravastatin therapy [PMID: 15548849]. SLCO1B1 variants have been associated with decreased fexofenedine and repaglinide AUC as well, though these observations remain preliminary because neither of these drugs is a known substrate of this transporter [PMID: 15842561, 15961978]. |
| Key PubMed IDs: | 10644574, 12130747 |
| Key Pathways: | Statin Pharmacokinetic Pathway |
| Drugs/Substrates: | pravastatin [PMID: 10601278], atorvastatin [PMID: 15970799], lovastatin [PMID: 15616150], cerivastatin [PMID: 15970799], pitavastatin [PMID: 15159445], bilirubin [PMID: 11134001, 10644574, 12670950]; SN-38 [PMID: 15608127], benzylpenicillin [PMID: 10873595], digoxin [PMID: 15994370], taurocholic acid [PMID: 10601278], dehydroepiandrosterone (DHEAS) [PMID: 10601278], estradiol 17-beta-glucaronide [PMID: 10358072], estrone-3-sulfate [PMID: 10358072], thyroid hormones (T4 and T3) [PMID: 10358072] estradiol [PMID: 10644574], leukotriene C4 and E4 [PMID: 10358072], thromboxane B2 [PMID: 10358072], prostaglandin E2 [PMID:10358072], arsenic [PMID: 16479312] |
| Important Variants: | SLC01B1:N130D, SLC01B1:V174A, SLC01B1:G-11187A |
| Important Haplotypes: | Genetic polymorphisms of human organic anion transporters OATP-C (SLC21A6) and OATP-B (SLC21A9): allele frequencies in the Japanese population and functional analysis. Nozawa T, Nakajima M, Tamai I, Noda K, Nezu J, Sai Y, Tsuji A, Yokoi T. J Pharmacol Exp Ther. 2002 Aug, 302(2):804-13. [PMID: 12130747]. SLCO1B1*1A , SLCO1B1*1B , SLCO1B1*5 , SLCO1B1*15, SLCO1B1*17 |