An article in Pharmacogenomics Journal puts the spotlight on the need to continue look for candidate genes and variants in many populations even when it seems as though current candidates explain a large amount of variability. [PMID: 30100615] identifies new candidate genes and variants that are important when the most well known variants are not present.
Rosuvastatin is a HMG-CoA reductase (HMGCR) inhibitor or statin, used in the treatment of high cholesterol and heart disease. The pharmacokinetics of individual statin drugs are influenced by their hydrophobicity, with the more hydrophobic statins being highly dependent on transporters for transport in and out of cells. Rosuvastatin is a hydrophobic statin and undergoes minimal metbolism with around 80% of drug dose excreted unchanged in feces [PMID: 14693307]. The transporter variants SLCO1B1 c.521T>C (rs4149056 p. Val174Ala) and ABCG2 c.421C>A (rs2231142, p. Gln141Lys) are key candidates in rosuvastatin PGx [PMID:16198652][PMID: 25630984]. Soko et al demonstrate that these variants differ in frequency in a range of African populations and are absent in some. They studied rosuvastatin PK in a group of individuals of Bantu decent and identified new variants in the SLCO1B1 and ABCG2 transporters and additional variants in other transporter genes and regulatory genes that influence transporter expression. PharmGKB will be updating our rosuvastatin PK pathway to include these new genes and variants.