The Frequency Of Rs2231142 in ABCG2 Among Native Hawaiian nd Pacific Islander Subgroups: Implications for Personalized Rosuvastatin Dosing

Abstract

Statins are among the most commonly prescribed medications worldwide. Rosuvastatin is a moderate- to high-intensity statin depending on the prescribed dose. Statin-associated muscle symptoms are the main side effects, contributing to low adherence to statins. The missense variant rs2231142 in ABCG2 affects the functionality of the ABCG2 transporter, altering the pharmacokinetics and pharmacodynamics of rosuvastatin. This special report aims to accentuate the importance of considering the ABCG2 genotype upon prescribing rosuvastatin in high cardiovascular disease risk subgroups, specifically Native Hawaiian and Pacific Islander populations. Based on the reported frequencies of rs2231142 in ABCG2, it may be justifiable to initiate low-dose rosuvastatin in Samoans relative to Marshallese or Native Hawaiians. Interpopulation differences in pharmacogenetic allele frequencies underscore the need to disaggregate broad population categories to achieve health equity in treatment outcomes.

Plain language summary

Rosuvastatin is a medication that is used to decrease levels of bad cholesterol in the blood. One of the side effects of rosuvastatin is muscle aches, which can cause patients to stop taking their medication. ABCG2 is a gene responsible for encoding ABCG2, an important transporter that plays a role in how the body interacts with many medications, including rosuvastatin. Genetic variations in ABCG2 result in a functional or nonfunctional transporter. This special report aims to focus on the importance of considering genetic variations in ABCG2 among different population subgroups, in particular Native Hawaiians, Samoans and Marshallese. The ABCG2 genotype could inform clinicians about the most effective rosuvastatin dose to prescribe. This approach highlights the importance of individualized patient characteristics above and beyond race and ethnicity.

Tweetable abstract

Starting low-dose rosuvastatin in Samoan versus Native Hawaiian and Marshallese may be needed. ABCG2 allele frequency within broad racial categories highlights the importance of interindividual variability and disaggregation of broad population groups.

Keywords::

• ABCG2
• adverse drug events
• drug transporter genes
• dyslipidemia
• Native Hawaiian
• Pacific Islanders
• pharmacogenetics
• racial minorities
• rosuvastatin
• statins

Financial & competing interests disclosure

This project was supported in part by the National Institute on Minority Health and Health Disparities (U54MD007584, G12MD007601) and the National Institute of General Medical Sciences (P20GM103466) of the NIH. The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

This project was supported in part by the National Institute on Minority Health and Health Disparities (U54MD007584, G12MD007601) and the National Institute of General Medical Sciences (P20GM103466) of the NIH. The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties. No writing assistance was utilized in the production of this manuscript.