OATP1B1

Overview

OATP1B1, also known as Organic Anion Transporting Polypeptide 1B1, is a protein encoded by the SLCO1B1 gene in humans. It is a member of the solute carrier organic anion transporter family and plays a crucial role in the hepatic uptake of a wide range of endogenous and exogenous compounds, including drugs, hormones, and toxins.

Structure

OATP1B1 is a transmembrane protein that is primarily expressed in the liver. It consists of 691 amino acids and has 12 predicted transmembrane domains. The protein is glycosylated and functions as a transporter by facilitating the movement of organic anions across the cell membrane.

Function

OATP1B1 is responsible for the uptake of various substrates from the blood into the liver. These substrates include:

• Bilirubin
• Bile acids
• Statins (e.g., atorvastatin, simvastatin)
• Antibiotics (e.g., rifampicin)
• Anticancer drugs (e.g., methotrexate)

The transport activity of OATP1B1 is essential for the hepatic clearance of these compounds, influencing their pharmacokinetics and pharmacodynamics.

Genetic Variability

The SLCO1B1 gene exhibits genetic polymorphisms that can significantly affect the function of OATP1B1. Notable polymorphisms include:

• SLCO1B1*5 (c.521T>C)
• SLCO1B1*15 (c.388A>G and c.521T>C)

These polymorphisms can lead to altered drug metabolism and increased risk of adverse drug reactions, particularly with statins, where they are associated with statin-induced myopathy.

Clinical Significance

OATP1B1 is clinically significant due to its role in drug-drug interactions and its impact on drug efficacy and toxicity. Inhibitors of OATP1B1 can lead to increased plasma concentrations of its substrates, potentially resulting in toxicity. Conversely, reduced function variants of OATP1B1 can lead to decreased drug clearance and increased risk of side effects.

Research and Development

OATP1B1 is a target for research in pharmacogenomics and personalized medicine. Understanding the genetic variability and regulation of OATP1B1 can help in predicting patient responses to drugs and in developing strategies to mitigate adverse effects.

Also see

• OATP1B3
• SLCO1B1 gene
• Pharmacogenomics
• Drug metabolism
• Hepatic transporters

External links

• NCBI Gene: SLCO1B1
• PharmGKB: SLCO1B1