2.1. Rotor syndrome

Mutations in the SLCO1B1 gene are involved in Rotor syndrome. This condition is characterized by elevated levels of bilirubin in the blood that can cause yellowing of the skin and whites of the eyes (jaundice). For this condition to occur, individuals must have mutations in the SLCO1B1 gene and a related gene called SLCO1B3. This related gene provides instructions for making a protein called OATP1B3, which has a similar transport function to OATP1B1. In some cases, the condition is caused by a deletion of genetic material that removes parts of both the SLCO1B1 and SLCO1B3 genes, so no functional OATP1B1 or OATP1B3 protein is made. Most mutations that cause Rotor syndrome lead to abnormally short, nonfunctioning OATP1B1 and OATP1B3 proteins. Without the function of either transport protein, bilirubin is less efficiently taken up by the liver and cleared from the body. The buildup of this substance leads to jaundice in people with Rotor syndrome.

2.2. Other disorders

Certain common variations (polymorphisms) in the SLCO1B1 gene are associated with a reduced ability to process certain drugs, including statins. The most widely studied polymorphism associated with this abnormality, which is found in approximately 15 percent of the population, changes a single protein building block in the OATP1B1 protein: the amino acid valine at position 174 is replaced with the amino acid alanine (written as V174A or SLCO1B1*5). The protein produced from this version of the SLCO1B1 gene is less able to transport compounds into the liver, which leads to elevated levels of the compounds in the body.

When statins are not efficiently transported into the liver, they build up in the body, and can cause a condition known as statin-induced myopathy. This condition causes fatigue, pain, tenderness, weakness, and cramping in muscles. People with the V174A polymorphism who take statin drugs have an increased risk of developing statin-induced myopathy.