The SLCO1B1 gene guides the creation of a specific protein. This protein plays a role in how the body handles various substances. Understanding this gene and its function clarifies how the body processes certain compounds, including medications.
The Function of the SLCO1B1 Gene
The SLCO1B1 gene provides instructions for making a protein known as organic anion transporting polypeptide 1B1, or OATP1B1. This protein acts as a specialized transporter, located on the surface of liver cells. Its main job is to move various substances from the bloodstream into the liver for processing and eventual removal from the body.
These transported substances include natural compounds produced by the body, such as bilirubin, a yellowish substance formed during the breakdown of red blood cells. OATP1B1 also facilitates the uptake of external compounds, including certain hormones, toxins, and a range of medications. This transport into the liver is necessary for these substances to be metabolized and cleared.
Genetic Variations and Their Impact
Genetic variations, also known as polymorphisms, can occur within the SLCO1B1 gene. These variations can alter the structure and, consequently, the efficiency of the OATP1B1 transporter protein. The most widely studied polymorphism, found in approximately 15% of the population, involves a change in a single protein building block within OATP1B1, leading to reduced transport ability.
These variations result in different functional groups, or phenotypes, for the OATP1B1 transporter. Individuals can have “normal function,” efficiently moving substances into the liver. Others may have “intermediate function,” where the transporter is somewhat less effective, or “poor function,” indicating a significantly reduced ability to transport substances.
Connection to Statin Medications
The functional differences in the OATP1B1 transporter, particularly “intermediate” and “poor function” phenotypes, have a direct connection to how the body processes statin medications. Statins are commonly prescribed to lower cholesterol levels, and their effectiveness relies on being transported into liver cells. When the OATP1B1 transporter is less efficient, statins are not moved from the bloodstream into the liver as quickly as they should be.
This slower clearance leads to higher concentrations of the statin drug remaining in the bloodstream. Elevated levels of statins in the blood significantly increase the risk of side effects, most notably muscle pain and weakness, known as myopathy. Simvastatin is the statin most strongly affected by SLCO1B1 variations. Individuals with a “poor function” SLCO1B1 genotype can experience a 3-to-17-fold increased risk of myopathy with statins, particularly simvastatin. For example, the risk of moderately severe to severe myopathy with 80 mg/day simvastatin is increased 5-fold to 3%.
While simvastatin is the primary example, other statins like atorvastatin and rosuvastatin are also affected, though typically to a lesser degree. Some statins, such as pravastatin and fluvastatin, are less dependent on the OATP1B1 pathway for their liver uptake, which can make them alternative choices for individuals with certain SLCO1B1 variations.
Implications for Other Medications
Beyond statins, variations in the SLCO1B1 gene can influence the processing of several other medications. Methotrexate, a drug used to treat certain cancers and autoimmune conditions, is also transported by OATP1B1. Genetic variations in SLCO1B1 have been linked to delayed methotrexate clearance and an increased risk of side effects, such as nausea.
Another medication affected is repaglinide, a drug prescribed for type 2 diabetes. Individuals with certain SLCO1B1 genotypes may experience higher blood concentrations of repaglinide, potentially increasing its effects. Generally, for these and other affected medications, a less efficient OATP1B1 transporter can lead to higher drug levels in the bloodstream, potentially increasing effects or side effects.
Discussing Results with a Healthcare Provider
Receiving genetic test results for SLCO1B1 provides valuable information, but it is not intended for self-diagnosis or for making independent changes to medication. This information serves as a tool for an informed discussion with a healthcare provider, such as a doctor, clinical pharmacist, or genetic counselor. These professionals can interpret the results within the context of an individual’s complete health profile, including existing medical conditions and other medications.
Healthcare providers can use SLCO1B1 genetic testing to help identify which medication or dose might be most appropriate. For instance, if a person is found to have a genetic variation that affects OATP1B1 function, the provider might consider adjusting a statin dose, prescribing an alternative statin, or monitoring more closely for potential side effects. This collaborative approach ensures that treatment decisions are tailored to the individual, aiming to optimize therapeutic benefits while minimizing risks.