Statins are widely used medications for the primary and secondary prevention of cardiovascular diseases. Statin-induced musculoskeletal symptoms are the primary adverse drug events contributing to poor adherence to lipid-lowering therapy. Rosuvastatin is characterized by interindividual differences in systemic exposure among different patient population subgroups. The missense variant Q141K within ABCG2, highly prevalent in some Asian subgroups, results in decreased transporter efflux function and increased exposure to rosuvastatin. We aim to highlight the implications of ABCG2 genotype in prescribing rosuvastatin and the ramifications of interpopulation differences in Q141K frequencies in the starting dose of rosuvastatin in major Asian subgroups, using the most recent genetic-based guidelines. The high frequency of Q141K in Filipinos could warrant a lower starting rosuvastatin dose versus non-Filipinos. The Q141K genotype frequencies in Asian subgroups suggest significant interpopulation differences, reinforcing the need to move beyond race-based to genotype-based rosuvastatin dosing.
Keywords: ABCG2; Asian ancestry; Filipinos; adverse drug reaction; cardiovascular pharmacogenomics; drug transporters; dyslipidemia; statins.
Rosuvastatin, a commonly prescribed cholesterol-lowering drug, has differences in response between different population subgroups. Rosuvastatin may also cause muscle pains, contributing to low adherence to the medication. Asians have a significantly high frequency of genetic variation (Q141K) within ABCG2, a critical rosuvastatin-efflux pump, leading to less functional transporter and higher drug levels. This special report highlights the role of ABCG2 genotyping in prescribing rosuvastatin. Also, it describes the consequences of between-population differences in the Q141K frequency in deciding the starting dose in individuals of Asian background, using the most recent genetic-based guidelines. Among different Asian subgroups, Filipinos have the highest Q141K polymorphism frequency and are more likely to require a lower starting dose of rosuvastatin than other Asians. Knowledge of the Q141K frequency in different Asian subgroups could drive individualized rosuvastatin dosing and reduce racial disparities in drug safety and efficacy.