The SLCO1B1 gene encodes the organic anion (group of compounds that include fatty acids, bile acids, and anionic drugs) transporting polypeptide 1B1 (OATP1B1), a liver-specific transmembrane receptor responsible for the sodium-independent uptake of various endogenous compounds (growing or originating from within an organism), including bilirubin, 17-beta-glucuronosyl estradiol, and leukotriene C4. Additionally, OATP1B1 plays a crucial role in the hepatic clearance (the rate at which the liver removes a substance from the blood) of several drug compounds, such as statins (known to lower LDL cholesterol levels in the blood), bromosulfophthalein (used to measure liver function), and rifampin (used to treat bacterial infections), by facilitating their transport from the bloodstream into hepatocytes for metabolism and excretion. SLCO1B1 decreased function can impair transporter activity, affecting drug pharmacokinetics (how the body processes a drug) and increasing the risk of adverse drug reactions.

The FDA has also specified a few drugs as they may result in higher concentrations in people who are poor or intermediate metabolizers of SLCO1B1. We have added two of the highlighted drugs, Atorvastatin (Lipitor) which belongs to statin class drugs, and Elagolix (Orilissa) which is a gonadotropin-releasing hormone (GnRH) antagonist used to treat moderate to severe pain caused by endometriosis.

Implications of Decreased SLCO1B1 Function

Genetic variations in SLCO1B1 can result in decreased transporter activity, leading to altered drug metabolism and increased susceptibility to adverse effects. Approximately 30% of individuals exhibit decreased SLCO1B1 function, while about 2.5% have poor function, significantly affecting drug clearance rates.

Impact on Statins

Statins, commonly prescribed for lowering cholesterol levels, are significantly affected by SLCO1B1 activity. Reduced function of OATP1B1 can lead to higher plasma concentrations of statins, increasing the risk of statin-induced myopathy. For instance, individuals with certain SLCO1B1 polymorphisms may experience up to a 130% increase in the area under the plasma-time curve (AUC) for statins, indicating higher systemic exposure.

Impact on Other Medications

Beyond statins, decreased SLCO1B1 function can influence the pharmacokinetics of various drugs across different therapeutic areas:

• Antidiabetic Drugs: Polymorphisms in SLCO1B1 may affect the transport and efficacy of certain oral antidiabetic medications, such as Repaglinide (Prandin), potentially altering therapeutic outcomes.
• Anticoagulants: Studies have indicated an association between SLCO1B1 polymorphisms and bleeding risks in patients receiving Edoxaban, an anticoagulant, suggesting that transporter function can influence drug safety profiles.
• Immunosuppressants: Research has shown that SLCO1B1 polymorphisms can significantly influence the pharmacokinetics of mycophenolic acid glucuronide in renal transplant recipients, potentially impacting drug efficacy and safety. Such as in the case of Tacrolimus (Prograf) SLCO1B1 variations may impact its hepatic uptake and plasma levels.

Pharmacogenomic Testing and RPh LABS

Pharmacogenomic testing offers valuable insights into an individual’s genetic profile, particularly concerning genes like SLCO1B1. By identifying specific polymorphisms, healthcare providers can predict how a patient may respond to certain medications, allowing for personalized drug selection and dosing. This approach minimizes the risk of adverse reactions and enhances therapeutic efficacy.

RPh Labs provides a non-invasive, at-home pharmacogenomic testing kit that requires only a saliva sample collected via a cheek swab. This convenient method enables individuals to gain insights into their genetic predispositions affecting drug metabolism. The results can guide healthcare providers in tailoring medication choices and dosages to align with the patient’s unique genetic makeup, optimizing treatment outcomes.

Conclusion

SLCO1B1 is a gene primarily responsible for transporting a group of compounds that include fatty acids, bile acids, and anionic drugs. It also carries endogenous compounds to the liver, where they are metabolized and either utilized in bodily processes or removed from the bloodstream through excretion. SLCO1B1 decreased function has significant consequences for drug metabolism and patient safety across various therapeutic areas. At-home Pharmacogenomic testing by RPh LABS provides a clear picture of your genome (all of your DNA), facilitating personalized medicine approaches with enhanced efficacy and reduced adverse effects.

References

https://medlineplus.gov/genetics/gene/slco1b1/
https://www.med.umich.edu/1libr/Pharmacy/PharmacogeneticTestingForSLCO1B1.pdf
https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2020.00728/
https://www.ncbi.nlm.nih.gov/gene/10599