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Review
. 2023 Jan;24(1):15-26.
doi: 10.2217/pgs-2022-0155. Epub 2023 Jan 18.

The frequency of rs2231142 in ABCG2 among Asian subgroups: implications for personalized rosuvastatin dosing

Khalifa Alrajeh  1   2 , Youssef M Roman  3
Affiliations
Review

The frequency of rs2231142 in ABCG2 among Asian subgroups: implications for personalized rosuvastatin dosing

Khalifa Alrajeh et al. Pharmacogenomics. 2023 Jan.

Abstract

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.

Plain language summary

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.

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Figures

Figure 1.
Figure 1.. A proposed model integrating factors affecting the response to rosuvastatin.
Figure 2.
Figure 2.. Implications of combined ABCG2 and SLCO1B1 phenotype in rosuvastatin starting dose using the 2022 CPIC guidelines.
ABCG2: Apical ATP-binding cassette transporter G2; SLCO1B1: Solute carrier organic anion transporter family member 1B1; CPIC: Clinical Pharmacogenetics Implementation Consortium; DF: Decreased function (yellow); NF: Normal function (green); PF: Poor function (gray); SAMS: Statin-associated musculoskeletal symptoms. * In all cases, the starting dose is recommended in the general population with the consideration of population-specific and disease-specific adjustment guidelines.
See this image and copyright information in PMC

References

    1. Cooper‐Dehoff RM, Niemi M, Ramsey LB et al. The Clinical Pharmacogenetics Implementation Consortium Guideline for SLCO1B1, ABCG2, and CYP2C9 genotypes and statin‐associated musculoskeletal symptoms. Clin. Pharmacol. Ther. 111(5). 1007–1021 (2022). - PMC - PubMed
    1. American College of Cardiology. Guidelines Made Simple | 2018 Blood Cholesterol Guideline (2018). https://www.acc.org/education-and-meetings/image-and-slide-gallery/media...
    1. Agency for Healthcare Research and Quality. Number of people with purchase in thousands by therapeutic class, United States, 1996 to 2020. Medical Expenditure Panel Survey (MEPS) (2020). https://www.ahrq.gov/data/meps.html
    1. ClinCalc. DrugStats Database (2021). https://clincalc.com/DrugStats/Top200Drugs.aspx
    1. The Most Prescribed Drugs in the US (2021). https://www.visualcapitalist.com/ranked-the-most-prescribed-drugs-in-the...

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